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Rizk SK, Farag AGA, Shaeir SMA. A study of granulysin and pentraxin 3 genetic polymorphisms and their contribution to acne susceptibility. Arch Dermatol Res 2024; 316:691. [PMID: 39412662 DOI: 10.1007/s00403-024-03444-9] [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: 08/04/2024] [Revised: 09/22/2024] [Accepted: 10/08/2024] [Indexed: 11/22/2024]
Abstract
This study aims to examine the genetic polymorphisms of the granulysin (GNLY) and pentraxin 3 (PTX3) genes and their association with acne in Egypt. Acne vulgaris is classified as a disorder of the pilosebaceous unit. Clinical, histological, and immunological findings indicate that inflammation is involved in every stage of acne development. GNLY and PTX3 are both involved in the body's immune system and may play a role in the pathophysiology of acne. This case-control study included 180 participants who have acne and 180 healthy controls. Real-time PCR was used to genotype GNLY rs7908 and PTX3 rs2305619 polymorphisms. Genotype occurrence and allelic spreading for both single nucleotide polymorphisms (SNP) are in Hardy-Weinberg equilibrium. Regarding rs7908, no statistical difference was observed in the genotype and allele distributions between acne patients and controls. On the other hand, rs2305619 showed a statistical difference in the genotype and allele distributions between acne patients and controls, with a marked prevalence of the GG group and G allele in acne patients. Our study revealed a significant link between the PTX3 rs2305619 and acne susceptibility in Egypt, with the AG + GG genotype strongly predicting acne. In contrast, the GNYL rs7908 polymorphism was not associated with acne. These results highlight a genetic component to acne and suggest that PTX3 rs2305619 could be a key marker for understanding acne susceptibility.
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Affiliation(s)
- Sara Kamal Rizk
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt.
| | - Azza Gaber Antar Farag
- Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
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Zeng X, Bahabayi A, Tuerhanbayi B, Zheng M, Liu T, Xu L, Long Y, Xia C, Lu S, Song Y, Liu C. The altered HLA-DQ expression in peripheral blood T cells of chronic hepatitis B patients characterizes the function of T cells. J Viral Hepat 2022; 29:340-351. [PMID: 35274405 DOI: 10.1111/jvh.13669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 01/28/2022] [Accepted: 02/22/2022] [Indexed: 12/09/2022]
Abstract
OBJECTIVE This study aimed to clarify the expression of HLA-DQ and granulysin in peripheral blood T-cell subsets in patients with chronic hepatitis B virus (CHB) and to evaluate their significance in assisting CHB diagnosis and immune status assessment. METHODS Peripheral blood from 34 CHB patients, 36 inactive HBsAg carriers and 33 healthy controls were collected, and HLA-DQ and granulysin in a series of T-cell subsets were analysed by flow cytometry. The ability to secrete IL-10 and IFN-γ and the functional T-cell subsets were measured in Treg and CD4 cells expressing HLA-DQ or not. Correlation analyses were further conducted between HLA-DQ/granulysin-related subsets and clinical indicators of HBV infection, and ROC curves were built to evaluate diagnosis efficiency of HLA-DQ-related subsets. RESULTS HLA-DQ+ percentages in circulating CD4 T cells were downregulated in CHB patients. The proportions of HLA-DQ + Tfh in CHB were upregulated while HLA-DQ+ percentages in Treg were decreased. In terms of function, the IFN-γ secretion ability of CD4 + T cells and IL-10 secretion in Tregs were stronger in HLA-DQ+ than HLA-DQ- subsets. HLA-DQ + CD4 + T cells and HLA-DQ + Treg were negatively correlated with HBV-DNA, while HLA-DQ + Tfh and Tfc cells were positively correlated with HBV-DNA and ALT. HLA-DQ + Treg/Tfh/Tfc could help to distinguish CHB from inactive HBsAg carriers. CONCLUSION HLA-DQ on T cells can characterize the function of T-cell subsets and analysis of HLA-DQ can help to evaluate immune status and assist in diagnosis of CHB.
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Affiliation(s)
- Xingyue Zeng
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Ayibaota Bahabayi
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | | | - Mohan Zheng
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Tianci Liu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Lijuan Xu
- Department of Immunology,School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Yan Long
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Changsheng Xia
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Songsong Lu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Ying Song
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Chen Liu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
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Khalid HN, Elghobashy YAE, Elsayed AN. GNLY Gene Polymorphism: A Potential Role in Understanding Psoriasis Pathogenesis. J Cosmet Dermatol 2022; 21:4805-4809. [DOI: 10.1111/jocd.14792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 10/28/2021] [Accepted: 01/11/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Hesham Nabil Khalid
- Dermatology Andrology & STDs department Faculty of Medicine Menoufia University Menoufia Egypt
| | | | - Asmaa Nagy Elsayed
- Resident of Dermatology Andrology &STDs at Ministry of Health Al‐Mahala El‐Kobra Al‐Gharbia Egypt
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Li J, Chen H, Chen J, Zhou B, Hou J, Jiang DK. A Missense Variant in Granulysin is Associated with the Efficacy of Pegylated-Interferon-Alpha Therapy in Chinese Patients with HBeAg-Positive Chronic Hepatitis B. Pharmgenomics Pers Med 2021; 14:1505-1515. [PMID: 34848996 PMCID: PMC8627316 DOI: 10.2147/pgpm.s337962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/03/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Granulysin (GNLY) is a cytotoxic granule that has been reported to have various antimicrobial activities. We evaluated the association between a missense variant in GNLY (rs11127) and treatment efficacy of pegylated interferon-alpha (PegIFNα) or nucleos(t)ide analogs (NUCs) in patients with chronic hepatitis B (CHB). PATIENTS AND METHODS We included a total of 1823 patients with hepatitis B e antigen (HBeAg)-positive CHB (954 patients treated with PegIFNα and 869 patients treated with NUCs) in four Phase IV multicenter randomized controlled trials. The association of the GNLY rs11127 genotype with the combined response (CR), defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA level <2000 IU/mL was evaluated. A polygenic score (PGS) was constructed to evaluate the cumulative effect of multiple single-nucleotide polymorphisms (SNPs), including rs11127 and several other SNPs, STAT4 rs7574865, CFB rs12614, and CD55 rs28371597, which were reported to be associated with CR. RESULTS GNLY rs11127 was significantly associated with CR in patients treated with PegIFNα. The CR rate in patients with the rs11127 CC genotype was higher than that with the CT or TT genotype (40.98% vs 30.34% or 27.09%, P = 0.003). Furthermore, a PGS integrating GNLY rs11127 and three other SNPs was significantly associated with CR in PegIFNα-treated patients (P < 0.001). However, no significant correlation was found between GNLY rs11127 and CR in NUCs-treated patients. CONCLUSION GNLY rs11127 is an independent biomarker for predicting the response to PegIFNα therapy in HBeAg-positive CHB patients. Furthermore, the PGS, including GNLY rs11127, provides new insights for individualized treatment in clinical practice.
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Affiliation(s)
- Jing Li
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Haitao Chen
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People’s Republic of China
| | - Jiaxuan Chen
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Bin Zhou
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - De-Ke Jiang
- State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
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Ermis E, Celik SK, Solak N, Genc GC, Dursun A. The role of GNLY gene polymorphisms in psoriasis pathogenesis. An Bras Dermatol 2019; 94:198-203. [PMID: 31090825 PMCID: PMC6486070 DOI: 10.1590/abd1806-4841.20198188] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 08/01/2018] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. The most accepted mechanism in the etiopathogenesis of psoriasis is the induction of inflammation with keratinocyte hyperproliferation. Granulysin (GNLY) is a cytolytic antimicrobial peptide (AMP) that is secreted together with granzyme and perforin from the granules of human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It has been immunohistochemically proven that the expression of granulysin is increased in lesions of psoriasis. OBJECTIVE This study aimed to investigate the relationship between psoriasis disease and granulysin gene polymorphisms. METHODS GNLY rs7908 and rs10180391 polymorphisms were studied by PCR-RFLP in 100 psoriasis patients under treatment in the Dermatology Polyclinic of Bulent Ecevit University. In addition, 100 healthy individuals with similar age and sex distribution were used as a control group. RESULTS In the control group, GNLY rs7908 CC genotype was significantly higher than in psoriasis patients (P= 0.031; OR= 0.305; Cl= 0.305 (0.121 - 0.773). In our study, the genotype distributions in patients and control groups were GNLY rs7908 (SNP) GG (51%, 37%), GC (41%, 44%), CC (8%, 19%); GNLY rs10180391 (SNP) from the CC (41%, 44%), CT (42%, % 41), TT (17%, 15%). STUDY LIMITATIONS The study only included Turkish patients. CONCLUSION Our findings showed that GNLY rs7908 CC genotype and C allele had a protective effect against psoriasis and decreased the disease severity (according to PASI score), whereas rs10180391 SNP did not show any effective role in psoriasis pathogenesis.
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Affiliation(s)
- Esra Ermis
- Department of Molecular Biology and Genetics, Faculty of
Sciences and Arts, Bulent Ecevit University, Zonguldak, Turkey
| | - Sevim Karakas Celik
- Department of Molecular Biology and Genetics, Faculty of
Sciences and Arts, Bulent Ecevit University, Zonguldak, Turkey
| | - Nilgun Solak
- Department of Dermatology, Faculty of Medicine, Bulent
Ecevit University, Zonguldak, Turkey
| | - Gunes Cakmak Genc
- Department of Medical Genetics, Faculty of Medicine,
Bulent Ecevit University, Zonguldak, Turkey
| | - Ahmet Dursun
- Department of Medical Genetics, Faculty of Medicine,
Bulent Ecevit University, Zonguldak, Turkey
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Quantitative assessment of HLA-DQ gene polymorphisms with the development of hepatitis B virus infection, clearance, liver cirrhosis, and hepatocellular carcinoma. Oncotarget 2017; 9:96-109. [PMID: 29416599 PMCID: PMC5787527 DOI: 10.18632/oncotarget.22941] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 11/03/2017] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B is one of the most common infectious diseases, which leads to public health problems in the world, especially in Asian counties. In recent years, extensive human genetic association studies have been carried out to identify susceptible genes and genetic polymorphisms to understand the genetic contributions to the disease progression of HBV infection. HLA-DQ gene variations have been reported to be associated with HBV infection/clearance, disease progression and the development of hepatitis B-related complications, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC). However, the results are either inconclusive or controversial. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Our data revealed that the HLA-DQ alleles rs2856718-G, rs7453920-A and rs9275319-G were significantly associated with decreased risk of HBV infection and HBV natural clearance. Logistic regression analyses showed that HLA-DQ alleles rs9275572-A significantly increased HBV infection clearance, and decreased HBV natural clearance. However, rs2856718-G and rs9275572-A were not associated with development of cirrhosis. The HLA-DQ polymorphisms (rs2856718 and rs9275572) were associated with a decreased HBV-related HCC risk in all genetic models, but rs9272105-A increased the risk of HBV-related HCC. In addition, no significant association was observed between HLA-DQ rs9275319-G polymorphism and HBV-related HCC. These stratified analyses were limited due to relatively modest size of correlational studies. In future, further investigation on a large population and different ethnicities are warranted. Our findings contribute to the personalized care and prognosis in hepatitis B.
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Association between HLA-DQ Gene Polymorphisms and HBV-Related Hepatocellular Carcinoma. Gastroenterol Res Pract 2017; 2017:7150386. [PMID: 28761441 PMCID: PMC5518512 DOI: 10.1155/2017/7150386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 05/23/2017] [Accepted: 06/08/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Host gene variants may influence hepatitis B virus- (HBV-) related HCC. Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Previous studies have investigated the HLA-DQ (rs2856718 and rs9275572) polymorphisms that may be associated with the development of HBV-related HCC. However, the results are controversial or inconclusive. Hence, we conducted a meta-analysis to derive a more precise estimation of the associations. A total of 6 articles were used to evaluate the effect of the two polymorphisms on the risk of HBV-related HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We found that rs2856718 and rs9275572 in HLA-DQ significantly decreased HBV-related HCC in total population, especially in Chinese, but not in Saudi Arabian. Further validation of our results in larger populations and different ethnicities are required.
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Li Y, Huang Q, Tang JT, Wei TT, Yan L, Yang ZQ, Bai YJ, Wang LL, Shi YY. Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients. Medicine (Baltimore) 2017; 96:e7205. [PMID: 28640108 PMCID: PMC5484216 DOI: 10.1097/md.0000000000007205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P = .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.
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Affiliation(s)
- Yi Li
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Qian Huang
- West China School of Medicine, Sichuan University
| | - Jiang-Tao Tang
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | | | - Lin Yan
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | | | - Yang-Juan Bai
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Lan-Lan Wang
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Yun-Ying Shi
- Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China
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Li F, Li X, Zou GZ, Gao YF, Ye J. Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese. World J Gastroenterol 2017; 23:1602-1607. [PMID: 28321161 PMCID: PMC5340812 DOI: 10.3748/wjg.v23.i9.1602] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/27/2016] [Accepted: 01/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection.
METHODS This study included 623 patients (495 males and 128 females) with chronic hepatitis B virus infection (CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the AccuCopy method. χ2 tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals (CIs) were used to estimate the effects of risk.
RESULTS Among male patients, there were significant differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy number of TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95%CI: 0.229-0.473, P < 0.001). Difference in TLR7 copy number was also found between AHB and CHB female patients, with low copy number again associated with an increased risk of chronic HBV infection (OR = 0.292, 95%CI: 0.173-0.492, P < 0.001). However, there were no significant differences in TLR7 copy number among the three types of chronic HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). In addition, there was no association between TLR7 copy number and titer of the HBV e antigen.
CONCLUSION Low TLR7 copy number is a risk factor for chronic HBV infection but is not associated with later stages of disease progression.
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Thuong PH, Tam DB, Sakurada S, Hang NTL, Hijikata M, Hong LT, Ngoc PTM, Anh PT, Cuong VC, Matsushita I, Lien LT, Keicho N. Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays. BMC Infect Dis 2016; 16:580. [PMID: 27756230 PMCID: PMC5070182 DOI: 10.1186/s12879-016-1911-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 10/11/2016] [Indexed: 12/03/2022] Open
Abstract
Background Granulysin (GNLY) is produced by human lymphocyte subpopulations and exhibits antimicrobial activity against Mycobacterium tuberculosis. We examined the association between GNLY levels in blood and latent tuberculosis (TB) infection. Methods Latency of TB infection among Vietnamese healthcare workers was estimated using interferon-gamma release assays (IGRA), and serum GNLY concentrations were measured using enzyme-linked immunosorbent assays. The levels of GNLY expression in whole blood and the presence of GNLY alleles with the exon-4 polymorphism rs11127 were also determined using PCR-based methods. Results Among 109 study participants, 41 (37.6 %) were IGRA positive and had significantly lower serum GNLY concentrations compared with IGRA-negative participants (adjusted mean, 95 % confidence interval; 2.03, 1.72–2.44 vs. 2.48, 2.10–2.92 ng/ml, P = 0.0127; analysis of covariance). Serum GNLY concentrations and TB antigen-stimulated interferon-gamma values were weakly inversely correlated (r = −0.20, P = 0.0333). Serum GNLY concentrations varied with GNLY genotypes even after adjustment for gender and age (adjusted P = 0.0015) and were moderately correlated with GNLY expression in blood cells (r = 0.40, P < 0.0001). In subsequent analyses, low serum GNLY concentrations were significantly associated with IGRA status (adjusted odds ratio and 95 % confidence interval, 0.55 and 0.31–0.98, respectively), although GNLY genotype and mRNA levels were not. Conclusions Decreased GNLY, presumably at the protein level, is linked to the immunological condition of latent TB infection.
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Affiliation(s)
| | - Do Bang Tam
- Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam
| | - Shinsaku Sakurada
- Bureau of International Medical Cooperation, National Center for Global Health and Medicine, Tokyo, Japan
| | | | - Minako Hijikata
- Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan
| | - Le Thi Hong
- Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam
| | | | - Pham Thu Anh
- Department of National Tuberculosis Program, Hanoi Lung Hospital, Hanoi, Vietnam
| | | | - Ikumi Matsushita
- Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan
| | | | - Naoto Keicho
- Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan.,National Center for Global Health and Medicine, Tokyo, Japan
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Wang L, Zou ZQ, Wang K. Clinical Relevance of HLA Gene Variants in HBV Infection. J Immunol Res 2016; 2016:9069375. [PMID: 27243039 PMCID: PMC4875979 DOI: 10.1155/2016/9069375] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 04/14/2016] [Indexed: 01/01/2023] Open
Abstract
Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.
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Affiliation(s)
- Li Wang
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, Shandong 264001, China
| | - Zhi-Qiang Zou
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, Shandong 264001, China
| | - Kai Wang
- Hepatology Department, Qilu Hospital of Shandong University, 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012, China
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Deltex1 Polymorphisms Are Associated with Hepatitis B Vaccination Non-Response in Southwest China. PLoS One 2016; 11:e0149199. [PMID: 26894927 PMCID: PMC4760674 DOI: 10.1371/journal.pone.0149199] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Accepted: 01/28/2016] [Indexed: 12/15/2022] Open
Abstract
Background Hepatitis B vaccination is the most important tool available for preventing hepatitis B virus (HBV) infection and reducing the prevalence of infection. However, epidemiological studies have demonstrated that morethan 5% of patients exhibit a non- or hypo-response to the HBV vaccine. Genetic variations associated with T cell immunity contribute to the immune response to HBV vaccination. The deltex 1 (DTX1) gene is involved in T cell anergy, which may also be associated with the immune response to the HBV vaccination. Methods We detected 10 single nucleotide polymorphisms (SNPs) in or around the DTX1 gene in 601 infants out of a population from Southwest China, including 299 high responders(HRs; HBsAb > 100 mIU/mL) and 302 non-responders (NRs; HBsAb < 10 mIU/mL). An additional validation study was performed, comprising 230 adult patients(135 HRs and 95 NRs) from Southwest China. Results This study found that the minor allele ‘G’ of rs2384077 (adjusted p = 2.63E-04,) and the minor allele ‘C’ of rs10744794 (adjusted p = 3.69E-04) in the first intron of the DTX1 gene were remarkably associated with the immune response to HBV vaccination in both infant and adult populations. Moreover, a subsequent analysis indicated that haplotypes (A-T, G-C) of the two SNPs were significantly associated with the immune response to HBV vaccination. Conclusions Two SNPs (rs2384077 and rs10744794) in an intron of DTX1 and the linkage disequilibrium (LD) block are significantly associated with the immune response to HBV vaccination. The functional element annotation of the LD block between the two SNPs contains four transcriptional regulatory elements. The results suggest that these two SNPs may be involved in the immune response to HBV vaccination.
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