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Liang L, Chen D, Han M, Liu LR, Luo L, Yue J. Impact of IL-32 gene polymorphisms on tuberculosis susceptibility in a Chinese Han population. Microb Pathog 2025; 200:107313. [PMID: 39842733 DOI: 10.1016/j.micpath.2025.107313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 12/26/2024] [Accepted: 01/18/2025] [Indexed: 01/24/2025]
Abstract
OBJECTIVE Interleukin (IL)-32, encoded by the IL-32 gene, is a crucial constituent of the autophagy pathway and is involved in the regulation of Mycobacterium tuberculosis (M.tb) infection, a major global health challenge. This study aimed to examine the potential association between IL-32 polymorphisms and susceptibility to Tuberculosis(TB), highlighting the significance of genetic factors in TB risk. DESIGN Sequence analysis of IL-32 was conducted in 570 individuals diagnosed with pulmonary tuberculosis (PTB), 363 individuals diagnosed with extrapulmonary tuberculosis (EPTB), and 604 healthy controls from the Chinese Han population, representing a broad spectrum of TB manifestations. Five single nucleotide polymorphisms(SNPs) were selected for analysis based on their potential impact on IL-32 function and TB susceptibility. RESULTS The study revealed that the polymorphism rs12934561C allele exhibits a positive correlation with elevated susceptibility to PTB (P = 0.003, OR (95%CI) = 1.28 (1.09-1.51)), highlighting its potential role as a biomarker for PTB risk. A noteworthy relationship was observed between the rs12934561 TT genotype and the decreased likelihood of PTB, further underscoring the complexity of IL-32's role in PTB susceptibility. Moreover, it was found that protective haplotypes for PTB are TCAAC (P = 0.001, OR (95%CI) = 0.75 (0.62-0.90)) and TCGTT (P = 0.002, OR (95%CI) = 0.47 (0.29-0.77)) may be present in IL-32; Conversely, the potential risk haplotypes for PTB are CCGAA (P = 0.007, OR (95%CI) = 1.29 (1.07-1.55)) and TCATT (P = 0.033, OR (95%CI) = 1.30 (1.02-1.66)), indicating genetic variations that increase PTB susceptibility. In contrast, neither allelic nor genotypic associations were statistically significant among EPTB cases, highlighting the distinct genetic influences on the different forms of TB. CONCLUSION In this study, we discovered that polymorphisms in IL-32 are significantly associated with increased susceptibility to pulmonary TB. This finding underscores the crucial role of genetic variation in the development of TB and provides a potential avenue for targeted interventions.
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Affiliation(s)
- Li Liang
- Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - DaWen Chen
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Min Han
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Li-Rong Liu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - LiuLin Luo
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
| | - Jun Yue
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
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Oliveira IBN, Nunes RV, Leite VRMC, Araújo CF, Silveira MB, Pinto SA, Lamounier LA, Borges CL, Martins E, Porto IDOP, Gomes RS, Ribeiro-Dias F. Single-nucleotide polymorphisms in genes associated with the vitamin D pathway related to clinical and therapeutic outcomes of American tegumentary leishmaniasis. Front Cell Infect Microbiol 2025; 14:1487255. [PMID: 39844838 PMCID: PMC11750871 DOI: 10.3389/fcimb.2024.1487255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 12/10/2024] [Indexed: 01/24/2025] Open
Abstract
Background The vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL). Methods The expressions of IFNG, IL15, IL32, CYP27B1, VDR, and other pro-inflammatory cytokines TNF, IL6, and IL17 genes were evaluated using real-time polymerase chain reaction (qPCR) in lesions of patients with localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). SNP genotypes/alleles (in IL15, IL32, CYP27B1, and VDR) were evaluated by TaqMan PCR assays using DNA from the blood of patients and healthy individuals. Serum vitamin D levels were determined by chemiluminescence. Results Vitamin D pathway-associated genes were expressed in cutaneous as well as mucosal lesions. IFNG, IL6, and IL17 were more highly expressed in ML than in LCL. In contrast, IL32γ/CYP27B1/VDR mRNAs were mainly correlated in LCL, and IL32γ in ML makes strong connections with all cytokines. The SNP IL32 rs1555001 was less frequent in patients with ML. In addition, some SNPs appear to influence the VDR and CYP27B1 (IL15 rs10519613 and IL15 rs3775597) and IL6 (VDR rs7975232) expressions in LCL and the IL17 expression in ML (IL15 rs3775597). Gene expression was also correlated with clinical parameters, such as number of lesions (CYP27B1 mRNA) and treatment failure (VDR mRNA). In addition, one SNP was associated with treatment failure in ML (VDR rs7975232). Conclusions Our findings suggested that some SNPs in the vitamin D pathway-associated genes can be related to resistance and therapeutic outcomes of ATL. They are promising candidates that need to be further evaluated to understand their biological effects in the control or immunopathogenesis of ATL.
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Affiliation(s)
- Iara Barreto Neves Oliveira
- Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
| | - Ramon Vieira Nunes
- Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
| | | | - Camila Freire Araújo
- Department of Infectious Diseases, Hospital de Doenças Tropicais Dr. Anuar Auad, Goiânia, Goiás, Brazil
| | - Murilo Barros Silveira
- Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
| | - Sebastião Alves Pinto
- Department of Anatomopathology, Instituto Goiano de Oncologia e Hematologia (INGOH), Goiânia, Goiás, Brazil
| | | | - Clayton Luiz Borges
- Laboratório de Biologia Molecular (LBM), Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
| | - Edésio Martins
- Department of Morphofunctional Axis, Universidade de Rio Verde, Goiânia, Goiás, Brazil
| | | | - Rodrigo Saar Gomes
- Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
| | - Fátima Ribeiro-Dias
- Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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Gautam A, Bhattacharyya C, Dasgupta A, Bhattacharjee S, Pandit B. A novel genetic association of IL32 with tuberculosis. Cytokine 2024; 184:156783. [PMID: 39442340 DOI: 10.1016/j.cyto.2024.156783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 09/27/2024] [Accepted: 10/11/2024] [Indexed: 10/25/2024]
Abstract
AIM IL32 is a pleiotropic intracellular cytokine with an emergent role in tuberculosis. The different isoforms of IL32: α, β, γ and δ have varying pro and anti-inflammatory potentials. We studied the role of genetic variants of IL32 and its isoforms in susceptibility to tuberculosis using a case-household contact association study. METHODOLOGY Using a targeted sequencing approach, IL32 (+1kb) gene was sequenced in 64 pairs of culture positive TB cases and their culture negative household contacts. Subsequently the identified variants were validated in an independent cohort of cases and household contacts using TaqMan genotyping assay. Regulatory role of the associated variants was assessed using GTExPortal, RegulomeDB score, HaploReg and ENCODE histone ChIP-seq data. Expression of IL32 and its isoforms was evaluated by RT-PCR in PBMC from unexposed healthy controls (N = 25) with different genotype background and stimulated with TB antigens ESAT6 and CFP10. ∼ 200 bp around the associated variant was cloned into pGL3 promoter vector to assess enhancer activity by dual luciferase assay in cell lines. RESULTS Intronic variant rs9927163(G/T) was found associated with pulmonary TB, T being the risk allele (OR = 2.3(1.40-3.83, p = 0.03)), while G is the protective allele. This finding was validated in independent set of TB cases and household contacts (p = 0.0435). rs9927163 is an eQTL for the genes IL32 (p = 4.1e-10) and BICDL2 (p = 2.1e-7) in whole blood and interrupts an AP-1 binding site. ENCODE histone ChIP-seq data shows rs9927163 residing within T cell specific H3K4me3 peak. The G allele is associated with greater enhancer activity in a T cell line (2.12 fold, p = 0.0059). The TT genotype showed greater normalized expression of IL32δ, a less proinflammatory isoform compared to the GT and GG genotypes together following ESAT6 (p = 0.02288) and CFP10 (p = 0.04595) treatment. This indicates that greater expression of a potentially less protective IL32 isoform within individuals with the TT genotype might be a risk factor for developing TB.
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Affiliation(s)
- Anuradha Gautam
- BRIC-National Institute of Biomedical Genomics (NIBMG), Kalyani, 741251, West Bengal, India
| | | | - Ahana Dasgupta
- BRIC-National Institute of Biomedical Genomics (NIBMG), Kalyani, 741251, West Bengal, India; Dr. Shroff's Charity Eye Hospital, Daryaganj, 110002, New Delhi, India
| | | | - Bhaswati Pandit
- BRIC-National Institute of Biomedical Genomics (NIBMG), Kalyani, 741251, West Bengal, India.
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Genetic Association between Polymorphisms of Interleukin-32 and Dilated Cardiomyopathy in Chinese Han Population. DISEASE MARKERS 2022; 2022:5946290. [PMID: 36505098 PMCID: PMC9733993 DOI: 10.1155/2022/5946290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 12/05/2022]
Abstract
Background Dilated cardiomyopathy is a primary myocardial disease and one of the critical causes of heart failure. It is the most common indication for heart transplantation worldwide, and most idiopathic dilated cardiomyopathies are sporadic and multifactorial. Evidence has supported that several inflammatory cytokines and immune responses are involved in its pathological process. Interleukin-32 is a proinflammatory cytokine and is elevated during the worsening cardiac function. Herein, we evaluated the correlation between interleukin-32 gene polymorphisms (rs12934561 and rs28372698) and the susceptibility to dilated cardiomyopathy. Methods We enrolled 418 dilated cardiomyopathy patients and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping the two single-nucleotide polymorphisms (SNPs), and SPSS software was used for statistical analyses. Results The C allele and CC genotype frequencies of rs12934561 were remarkably elevated in dilated cardiomyopathy patients compared to controls (both P < 0.001). The A allele and AA genotype frequencies of rs28372698 significantly decreased in dilated cardiomyopathy patients (P = 0.004 and P = 0.02, respectively). Compared to TT/TC genotype carriers of rs12934561, CC homozygotes presented an increased risk of dilated cardiomyopathy when the left ventricular ejection fraction no more than 30% (P = 0.02). Conclusions The IL-32 gene polymorphisms might implicate in DCM risk in the Chinese Han population, and rs12934561 could be a potential forecasting factor for screening high-risk population for DCM.
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Mazlum F, Gharesi-Fard B, Hadinedoushan H, Bakhshizadeh Ghashti Y. Association between interleukin-32 gene polymorphism and susceptibility to preeclampsia. Hypertens Pregnancy 2021; 40:218-225. [PMID: 34346819 DOI: 10.1080/10641955.2021.1958836] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To determine association between IL-32 gene polymorphism, and serum levels of IL-32 and susceptibility to preeclampsia (PE). METHODS The frequency of IL-32 rs9927163 and rs4786370 polymorphisms was determined by PCR-RFLP. Also ELISA was used to determine the levels of serum IL-32. RESULTS Regarding rs4786370 C/T SNPs, the frequencies of CT, TT genotypes, and T allele were shown to be higher in the PE patients. IL-32 serum level significantly increased in the PE patients. CONCLUSION Variety of allele and genotype IL32 rs4786370 as well as a rise in serum level of IL-32 can be regarded as a risk factor for PE.
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Affiliation(s)
- Fatemeh Mazlum
- Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Behrouz Gharesi-Fard
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Hadinedoushan
- Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Impact of interleukin-32 germ-line rs28372698 and intronic rs12934561 polymorphisms on cancer development: A systematic review and meta-analysis. Int Immunopharmacol 2021; 99:107964. [PMID: 34271417 DOI: 10.1016/j.intimp.2021.107964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/21/2021] [Accepted: 07/05/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE The pro-inflammatory cytokine IL-32 has high susceptibility to develop cancer. But no previous meta-analysis was done to provide firm evidence. This systematic review and meta-analysis was designed to evaluate the association of IL-32 gene polymorphisms (rs28372698 and rs12934561) with cancer. METHOD Eligible studies were selected using authentic databases searching from January 2013 to January 2021. Demographic data and genotypic information were extracted and organized from the selected studies. Review Manager (RevMan) version 5.4 was used to perform data analysis and data arrangement for meta-analysis. RESULTS A total of seven studies with 3395 patients and 3781 controls were included in this study. IL-32 rs28372698 polymorphism implied that mutant allele (TT) carriers had a significantly higher risk of cancer (OR = 1.43, p = 0.032). Codominant 3, recessive and allele models also showed 1.36-, 1.38- and 1.11-fold increased risk, respectively (p < 0.05). Besides, the Asian population showed a significantly increased risk in codominant 2 (OR = 1.74), codominant 3 (OR = 1.78), recessive (OR = 1.76) and allele model (OR = 1.16). IL-32 rs12934561 showed significantly reduced cancer risk in codominant 1 (OR = 0.66. p = 0.035), codominant 2 (OR = 0.76, p = 0.007), and dominant model (OR = 0.72, p = 0.012). After subgroup analysis, an association of rs12934561 was found in Asians (codominant 1: OR = 0.54, p = 7.28 × 10-8; codominant 2: OR = 1.40, p = 0.019; codominant 3: OR = 0.76, p = 0.0006; dominant model: OR = 0.64, p = 1.12 × 10-5; overdominant model: OR = 0.64, p = 3.92 × 10-7) but not in Caucasians. After stratifying with the control source, a significant (p < 0.05) association of rs28372698 and rs12934561 was found with cancer in population-based controls. No publication bias was found, and the outcome of this meta-analysis was not influenced by any individual study confirmed from sensitivity analysis. Moreover, trial sequential analysis (TSA) established a link between rs28372698 and rs12934561 polymorphisms and cancer. CONCLUSION The outcome of this meta-analysis revealed that IL-32 rs28372698 and rs12934561 polymorphisms are associated with cancer. Moreover, the Asian dynasty had a significant association compared to Caucasians.
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7
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IL32: The multifaceted and unconventional cytokine. Hum Immunol 2021; 82:659-667. [PMID: 34024634 DOI: 10.1016/j.humimm.2021.05.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 04/20/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023]
Abstract
Interleukin 32 is a unique intracellular cytokine which affects many cellular and physiological functions like cell death and survival, inflammation and response to pathogens. With numerous transcripts, more than one biologically active isoforms, IL32 drives its effect in diverse cellular functions. A cytokine restricted to higher mammals, it is known to fine tune multiple pathways involved in metabolic processes or infection. It modulates the immune response against diverse pathogens like Leishmania, Mycobacterium and HIV. IL32 has been associated with cancers of inflammatory nature too. It also plays an important role in chronic inflammatory diseases like RA, lung and airway disease like COPD. In this review we have discussed about identification and characterization of this non classical cytokine IL32, its structure and function at gene as well as at protein level, isoforms and their diverse functions. Role of IL32 in multiple diseases and particularly mycobacterial disease has been highlighted here. We have also summarised the genetic variants present in the IL32 gene and it's promoter region. Association of these variants, with cellular phenotype, patho-physiological conditions in different disease have also been discussed here.
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Alehagen U, Shamoun L, Dimberg JI, Wågsäter D. Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32. Exp Ther Med 2020; 21:127. [PMID: 33376509 PMCID: PMC7751449 DOI: 10.3892/etm.2020.9559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 09/09/2020] [Indexed: 12/12/2022] Open
Abstract
One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.
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Affiliation(s)
- Urban Alehagen
- Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
| | - Levar Shamoun
- Division of Medical Diagnostics, Department of Laboratory Medicine, Jönköping County, SE-553 05 Jönköping, Sweden.,Department of Medical Cell Biology, Uppsala University, SE-752 36 Uppsala, Sweden
| | - Jan Ingvar Dimberg
- Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, SE-553 18 Jönköping, Sweden
| | - Dick Wågsäter
- Department of Medical Cell Biology, Uppsala University, SE-752 36 Uppsala, Sweden
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Admission IL-32 concentration predicts severity and mortality of severe community-acquired pneumonia independently of etiology. Clin Chim Acta 2020; 510:647-653. [PMID: 32860786 DOI: 10.1016/j.cca.2020.08.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 08/13/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Severe community-acquired pneumonia (SCAP) is a critical disorder with high morbidity and mortality, usually manifested as acute respiratory failure and septic shock generally caused by exaggerated systemic inflammation. Interleukin-32 (IL-32), a pro-inflammatory cytokine, has been reported involved in various infectious diseases. We investigated the efficacy of the plasma IL-32 as a biomarker for evaluating the severity and clinical outcomes in SCAP patients. METHODS A total of 124 adult immunocompetent SCAP patients and 87 healthy controls were enrolled in this observational, prospective cohort study. RESULTS We found that PBMCs IL-32 mRNA and plasma IL-32 concentrations on admission of SCAP patients were significantly higher than healthy controls. Plasma IL-32 concentrations closely correlated with increasing severity scores, the need for vasopressor support or invasive mechanical ventilation but not with the etiology. The area under the curve (AUC) for predicting 30-day mortality using IL-32 was 0.812, is superior to WBCs and CRP. Incorporation of IL-32 with the severity scores were shown to improve the prognostic accuracy considerably. Furthermore, the 30-day cumulative survival rate in high IL-32 concentration group was significantly lower than that in the low concentration group. In a multivariate Cox regression analysis, higher IL-32 concentration and higher PSI score were recognized as the independent risk factors for survival, and the relative risks were 2.568 and 3.362, respectively. CONCLUSIONS Admission IL-32 concentration closely related to the severity and mortality of SCAP, and it may be served as a potential biomarker to help clinical judgment and management.
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Tuan NM, Lee CH. Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target. Cancers (Basel) 2020; 12:E1600. [PMID: 32560530 PMCID: PMC7353083 DOI: 10.3390/cancers12061600] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/04/2020] [Accepted: 06/08/2020] [Indexed: 01/21/2023] Open
Abstract
Anillin (ANLN), an actin-binding protein, reportedly plays a vital role in cell proliferation and migration, particularly in cytokinesis. Although there have been findings pointing to a contribution of ANLN to the development of cancer, the association of ANLN to cancer remains not fully understood. Here, we gather evidence to determine the applicability of ANLN as a prognostic tool for some types of cancer, and the impact that ANLN has on the hallmarks of cancer. We searched academic repositories including PubMed and Google Scholar to find and review studies related to cancer and ANLN. The conclusion is that ANLN could be a potent target for cancer treatment, but the roles ANLN, other than in cytokinesis and its influence on tumour microenvironment remodeling in cancer development, must be further elucidated, and specific ANLN inhibitors should be found.
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Affiliation(s)
| | - Chang Hoon Lee
- College of Pharmacy, Dongguk University, Seoul 04620, Korea;
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Morsaljahan Z, Rafiei A, Valadan R, Abedini M, Pakseresht M, Khajavi R. Association between interleukin-32 polymorphism and multiple sclerosis. J Neurol Sci 2017; 379:144-150. [PMID: 28716229 DOI: 10.1016/j.jns.2017.05.045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 04/29/2017] [Accepted: 05/22/2017] [Indexed: 11/29/2022]
Affiliation(s)
- Zaher Morsaljahan
- Department of Immunology, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Alireza Rafiei
- Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Reza Valadan
- Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mahmoud Abedini
- Department of Neurology, Buali Sina Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Masoumeh Pakseresht
- Department of Immunology, Mazandaran University of Medical Sciences, Sari, Iran
| | - Rezvan Khajavi
- Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Holopainen S, Hytönen MK, Syrjä P, Arumilli M, Järvinen AK, Rajamäki M, Lohi H. ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs. PLoS Genet 2017; 13:e1006625. [PMID: 28222102 PMCID: PMC5340406 DOI: 10.1371/journal.pgen.1006625] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 03/07/2017] [Accepted: 02/09/2017] [Indexed: 01/24/2023] Open
Abstract
Acute respiratory distress syndrome (ARDS) is the leading cause of death in critical care medicine. The syndrome is typified by an exaggerated inflammatory response within the lungs. ARDS has been reported in many species, including dogs. We have previously reported a fatal familial juvenile respiratory disease accompanied by occasional unilateral renal aplasia and hydrocephalus, in Dalmatian dogs. The condition with a suggested recessive mode of inheritance resembles acute exacerbation of usual interstitial pneumonia in man. We combined SNP-based homozygosity mapping of two ARDS-affected Dalmatian dogs and whole genome sequencing of one affected dog to identify a case-specific homozygous nonsense variant, c.31C>T; p.R11* in the ANLN gene. Subsequent analysis of the variant in a total cohort of 188 Dalmatians, including seven cases, indicated complete segregation of the variant with the disease and confirmed an autosomal recessive mode of inheritance. Low carrier frequency of 1.7% was observed in a population cohort. The early nonsense variant results in a nearly complete truncation of the ANLN protein and immunohistochemical analysis of the affected lung tissue demonstrated the lack of the membranous and cytoplasmic staining of ANLN protein in the metaplastic bronchial epithelium. The ANLN gene encodes an anillin actin binding protein with a suggested regulatory role in the integrity of intercellular junctions. Our study suggests that defective ANLN results in abnormal cellular organization of the bronchiolar epithelium, which in turn predisposes to acute respiratory distress. ANLN has been previously linked to a dominant focal segmental glomerulosclerosis in human without pulmonary defects. However, the lack of similar renal manifestations in the affected Dalmatians suggest a novel ANLN-related pulmonary function and disease association.
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Affiliation(s)
- Saila Holopainen
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
- The Folkhälsan Institute of Genetics, Helsinki, Finland
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
| | - Marjo K. Hytönen
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
- The Folkhälsan Institute of Genetics, Helsinki, Finland
| | - Pernilla Syrjä
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
| | - Meharji Arumilli
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
- The Folkhälsan Institute of Genetics, Helsinki, Finland
| | - Anna-Kaisa Järvinen
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
| | - Minna Rajamäki
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
| | - Hannes Lohi
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
- The Folkhälsan Institute of Genetics, Helsinki, Finland
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Wang Y, Yang Y, Zhu Y, Li L, Chen F, Zhang L. Polymorphisms and expression of IL-32: impact on genetic susceptibility and clinical outcome of lung cancer. Biomarkers 2016; 22:165-170. [PMID: 27775437 DOI: 10.1080/1354750x.2016.1252956] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Yanwen Wang
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
| | - Yongfeng Yang
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
| | - Yihan Zhu
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
| | - Li Li
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
| | - Fei Chen
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
| | - Li Zhang
- Laboratory of Pathology, Department of Pathology, West China Hospital Sichuan University, Chengdu, P.R. China
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Association of Plasma IL-32 Levels and Gene Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population. DISEASE MARKERS 2016; 2016:2460206. [PMID: 27069296 PMCID: PMC4789414 DOI: 10.1155/2016/2460206] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 01/26/2016] [Accepted: 02/09/2016] [Indexed: 02/05/2023]
Abstract
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. IL-32, a secreted protein, has been reported to be associated with several autoimmune diseases. Our preliminary experiment showed different plasma IL-32 levels than that mentioned in a published report on the same population. In order to elucidate the correlation between IL-32 and SLE, we determined the plasma level and two single nucleotide polymorphisms (SNPs) of IL-32 in 152 patients with SLE and 310 healthy controls and analyzed the relationship based on the clinical parameters. The results showed that plasma IL-32 levels in patients with SLE were markedly lower than that in the healthy controls. In the SLE group, patients with detectable IL-32 presented low serum C3 concentrations. Further studies indicated that the rs28372698 SNP was associated with the susceptibility to SLE. Taken together, our results suggested that IL-32 could possibly be a candidate marker to monitor SLE disease stability and screening in future.
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Hadade A, Ionescu D, Mocan T, Necula A, Cristea V. Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa. J Crit Care Med (Targu Mures) 2016; 2:44-50. [PMID: 29967836 DOI: 10.1515/jccm-2016-0008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 12/18/2015] [Indexed: 11/15/2022] Open
Abstract
Introduction It has been reported that as compared with total intravenous anesthesia (TIVA), inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.The aim of the study is to investigate if there is an in-vivo relationship between proinflammatory cytokines, Interleukin-32 (IL-32) and Tumour necrosis factor - α (TNF-α), in patients undergoing laparoscopic cholecystectomies with two different anesthetic techniques, TIVA or inhalation anesthesia. Material and Methods Twenty two consecutive patients undergoing laparoscopic cholecystectomies were prospectively randomized into two groups: Group 1: TIVA with target-controlled infusion (TIVA-TCI) (n=11) and Group 2: isoflurane anesthesia (ISO) (n=11). IL-32 and TNF-α were determined before the induction of anesthesia (T1), before incision (T2) and at 2h (T3) and 24h (T4) postoperatively. Our primary outcome was to compare plasma levels of IL-32 and TNF-α concentrations (expressed as area-under-the-curve) over 24 hours between study groups. Our secondary outcome was to establish whether there is a correlation between plasma levels of IL-32 and of TNF-α at each time point between the two groups. Results Area-under-the-curve (AUC) of IL-32 plasma concentration was 7.53 in Group 1 (TIVA) versus 3.80 in Group 2 (ISO), p= 1. For TNF-α, AUC of plasma concentration was 733.9 in Group 1 (TIVA) and 668.7 in Group 2 (ISO), p=0.066. There were no significant differences in plasma concentrations of both IL-32 and TNF-α between the groups. Conclusions IL-32 expression in response to minor surgery is very low. There were no significant difference between plasma levels of TNF-α and IL-32 after TIVA versus inhalation anesthesia during the first 24 hours postoperatively. Further studies are needed on larger groups to investigate whether there can be a correlation between these interleukins after 2 different anesthetic techniques and the impact of this correlation on postoperative outcome.
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Affiliation(s)
- Adina Hadade
- Department of Anesthesia and Intensive Care, "IuliuHatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniela Ionescu
- Department of Anesthesia and Intensive Care, "IuliuHatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Teodora Mocan
- Department of Physiology, "IuliuHatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Alexandru Necula
- Department of Surgery, Regional Institute for Gastroenterology and Hepatology "Prof dr Octavian Fodor", Cluj-Napoca, Romania
| | - Victor Cristea
- Department of Clinical Immunology, "IuliuHatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Ota K, Kawaguchi M, Fujita J, Kokubu F, Huang SK, Morishima Y, Matsukura S, Kurokawa M, Ishii Y, Satoh H, Sakamoto T, Hizawa N. Synthetic double-stranded RNA induces interleukin-32 in bronchial epithelial cells. Exp Lung Res 2015; 41:335-43. [DOI: 10.3109/01902148.2015.1033569] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Li D, Chen D, Zhang X, Wang H, Song Z, Xu W, He Y, Yin Y, Cao J. c-Jun N-terminal kinase and Akt signalling pathways regulating tumour necrosis factor-α-induced interleukin-32 expression in human lung fibroblasts: implications in airway inflammation. Immunology 2015; 144:282-90. [PMID: 25157456 DOI: 10.1111/imm.12374] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 08/19/2014] [Accepted: 08/20/2014] [Indexed: 12/22/2022] Open
Abstract
Airway inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are associated with elevated expression of interleukin-32 (IL-32), a recently described cytokine that appears to play a critical role in inflammation. However, so far, the regulation of pulmonary IL-32 production has not been fully established. We examined the expression of IL-32 by tumour necrosis factor-α (TNF-α) in primary human lung fibroblasts. Human lung fibroblasts were cultured in the presence or absence of TNF-α and/or other cytokines/Toll-like receptor (TLR) ligands or various signalling molecule inhibitors to analyse the expression of IL-32 by quantitative RT-PCR and ELISA. Next, activation of Akt and c-Jun N-terminal kinase (JNK) signalling pathways was investigated by Western blot. Interleukin-32 mRNA of four spliced isoforms (α, β, γ and δ) was up-regulated upon TNF-α stimulation, which was associated with a significant IL-32 protein release from TNF-α-activated human lung fibroblasts. The combination of interferon-γ and TNF-α induced enhanced IL-32 release in human lung fibroblasts, whereas IL-4, IL-17A, IL-27 and TLR ligands did not alter IL-32 release in human lung fibroblasts either alone, or in combination with TNF-α. Furthermore, the activation of Akt and JNK pathways regulated TNF-α-induced IL-32 expression in human lung fibroblasts, and inhibition of the Akt and JNK pathways was able to suppress the increased release of IL-32 to nearly the basal level. These data suggest that TNF-α may be involved in airway inflammation via the induction of IL-32 by activating Akt and JNK signalling pathways. Therefore, the TNF-α/IL-32 axis may be a potential therapeutic target for airway inflammatory diseases.
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Affiliation(s)
- Dagen Li
- Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China
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Significant association between IL-32 gene polymorphisms and susceptibility to endometrial cancer in Chinese Han women. Tumour Biol 2015; 36:5265-72. [PMID: 25663496 DOI: 10.1007/s13277-015-3186-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 01/27/2015] [Indexed: 01/27/2023] Open
Abstract
Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32-4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036-1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05-2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011-1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.
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Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst. Cell Mol Immunol 2014; 12:633-44. [PMID: 25176527 DOI: 10.1038/cmi.2014.80] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 07/29/2014] [Accepted: 07/30/2014] [Indexed: 02/07/2023] Open
Abstract
Influenza A virus (IAV) infection is a major worldwide public health problem. However, the factors involved in mediating the inflammatory response to this infection and their relationships remain poorly understood. Here, we show that IAV infection stimulates the expression of the soluble IL-6 receptor (sIL-6R), a multifunctional protein involved in IL-6 signaling. Interestingly, sIL-6R expression upregulated the levels of its own ligand, IL-6 and those of the pro-inflammatory cytokine IL-32. shRNA-mediated knockdown of sIL-6R suppressed IL-6 and IL-32, indicating that this regulation is dependent on sIL-6R during IAV infection. Furthermore, our results demonstrate that IL-32 participates in a negative feedback loop that inhibits sIL-6R while upregulating IL-6 expression during IAV infection. Therefore, we show that sIL-6R is a critical cellular factor involved in the acute inflammatory response to viral infection.
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Wacharasint P, Nakada TA, Boyd JH, Russell JA, Walley KR. AA genotype of IL-8 -251A/T is associated with low PaO(2)/FiO(2) in critically ill patients and with increased IL-8 expression. Respirology 2013; 17:1253-60. [PMID: 22897124 DOI: 10.1111/j.1440-1843.2012.02244.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVE Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) -251A/T in its promoter region. We hypothesized that IL-8 -251A/T SNP is associated with PaO(2)/FiO(2) in critically ill patients. METHODS We conducted genetic-association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 -251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO(2) /FiO(2) < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. RESULTS The frequency of the patients with PaO(2)/FiO(2) <200 was significantly greater in patients who had the AA genotype of -251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype (P = 0.022). CONCLUSIONS Critically ill Caucasian patients who had the AA genotype of IL-8 -251A/T had an increased risk of PaO(2)/FiO(2) <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes.
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Affiliation(s)
- Petch Wacharasint
- University of British Columbia, Critical Care Research Laboratories, Institute for Heart+Lung Health, St. Paul's Hospital, Vancouver, BC, Canada
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Plantinga TS, Costantini I, Heinhuis B, Huijbers A, Semango G, Kusters B, Netea MG, Hermus ARMM, Smit JWA, Dinarello CA, Joosten LAB, Netea-Maier RT. A promoter polymorphism in human interleukin-32 modulates its expression and influences the risk and the outcome of epithelial cell-derived thyroid carcinoma. Carcinogenesis 2013; 34:1529-35. [DOI: 10.1093/carcin/bgt092] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
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Song Z, Yao C, Yin J, Tong C, Zhu D, Sun Z, Jiang J, Shao M, Zhang Y, Deng Z, Tao Z, Sun S, Bai C. Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury. J Transl Med 2012; 10:166. [PMID: 22901274 PMCID: PMC3478205 DOI: 10.1186/1479-5876-10-166] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Accepted: 07/09/2012] [Indexed: 12/31/2022] Open
Abstract
Background Recent studies showed that overwhelming inflammatory response mediated by the toll-like receptor (TLR)-related pathway was important in the development of acute lung injury (ALI). The aim of this study was to determine whether common genetic variation in four genes of the TLR signaling pathway were associated with sepsis-induced ALI susceptibility and risk of death in Chinese Han population. Methods Fourteen tag single nucleotide polymorphisms (tagSNPs) in MyD88, IRAK1, IRAK4 and TRAF6 were genotyped in samples of sepsis-induced ALI (n = 272) and sepsis alone patients (n = 276), and tested for association in this case-control collection. Then, we investigated correlation between the associated SNP and the mRNA expression level of the corresponding gene. And we also investigated correlation between the associated SNP and tumor necrosis factor alpha (TNF-α) as well as interleukin-6 (IL-6) concentrations in peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharides (LPS) ex vivo. The mRNA expression level was determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results The association analysis revealed that rs4755453, an intronic SNP of TRAF6, was significantly associated with susceptibility to sepsis-induced ALI. The C allele frequency of rs4755453 in the sepsis alone group was significantly higher than that in the sepsis-induced ALI group (P = 0.00026, odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.37–0.74). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. TRAF6 mRNA expression levels in PBMCs from homozygotes of the rs4755453G allele were significantly higher than that in heterozygotes and homozygotes of the rs4755453C allele at baseline (P = 0.012 and P = 0.003, respectively) as well as after LPS stimulation (P = 0.009 and P = 0.005). Moreover, the concentrations of TNF-α and IL-6 in cell culture supernatants were also significantly higher in the subjects with rs4755453GG genotype than in subjects with CG and CC genotype. None of the 14 tagSNPs showed associations with risk of death and severity among ALI cases. Conclusions Our findings indicated that common genetic variants in TRAF6 were significantly associated with susceptibility to sepsis-induced ALI in Chinese Han population. This was the first genetic evidence supporting a role for TRAF6 in ALI.
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Affiliation(s)
- Zhenju Song
- Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
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