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Ye C, Hu Z, Wu E, Yang X, Buford UJ, Guo Z, Saveanu RV. Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis. J Psychiatr Res 2016; 81:56-62. [PMID: 27380186 DOI: 10.1016/j.jpsychires.2016.06.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/23/2016] [Accepted: 06/10/2016] [Indexed: 12/14/2022]
Abstract
The aim of this meta-analysis is to assess the associations between two most widely investigated polymorphisms (rs3746544 and rs1051312) in the 3'UTR of the SNAP-25 gene and susceptibility of ADHD. Two investigators selected related studies and assessed methodological quality independently. Six studies were included in this meta-analysis for a total of 715 cases and 655 controls. There is no apparent association between rs3746544 polymorphisms and risk of ADHD. However, subgroup analysis based on ethnicity demonstrated a strong association between rs3746544 polymorphism and ADHD in the subset of Asian participants, but not among Caucasians. Compared to the T allele, the allele G was associated with a significantly decreased risk of developing ADHD in the Asian population (odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.52-0.95, p = 0.02). The association between the TT genotype and ADHD risk was also significantly increased as compared to G/T (OR = 1.56, 95% CI = 1.00-2.44, p = 0.05) and the dominant genetic model (GG + GT vs. TT: OR = 1.51, 95% CI = 1.07-2.13, p = 0.02). For the rs1051312 SNP, being homozygous for the minor allele (C/C) was associated with a 3.66 higher odds of ADHD as compared to cases homozygous for the major allele (T/T) (95% CI = 1.64-8.13, p = 0.001), and 3.57 higher odds as compared to heterozygous (C/T) carriers (95% CI = 2.01-12.90, p < 0.001). Our results suggest that the polymorphisms rs3746544 and rs1051312 may increase the odds of developing ADHD. Additional studies are needed to confirm these findings.
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Affiliation(s)
- Chuanzhong Ye
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States.
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, Fujian Medical University, 1 Xue Yuan Road University Town, Fujian, 350108, China
| | - Evan Wu
- Department of Health Sciences, University of Miami Miller School of Medicine, 1120 NW 14th St, Miami, FL, 33136, United States
| | - Xiaolu Yang
- Department of Epidemiology and Health Statistics, Fujian Medical University, 1 Xue Yuan Road University Town, Fujian, 350108, China
| | - Ushimbra J Buford
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
| | - Zhihong Guo
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
| | - Radu V Saveanu
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
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Yuan L, Zhang TT, Ren Y. miR-27a rs895819 polymorphism and risk of cancer in Chinese population: a meta-analysis. J Evid Based Med 2015; 8:75-83. [PMID: 25976406 DOI: 10.1111/jebm.12152] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 03/24/2015] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Previous studies have evaluated the association between miR-27a rs895819 polymorphism and cancer risk in Chinese population, but the results were inconclusive. The present meta-analysis was conducted to clarify these controversies. METHODS A comprehensive search was conducted to identify all relevant case-control studies of miR-27a rs895819 polymorphism and cancer risk in Chinese participants. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. RESULTS A total of 12 case-control studies involving 2655 cases and 3106 controls were included. Overall, the results suggested that there was no significant association between miR-27a rs895819 polymorphism and cancer risk in Chinese population (OR = 1.14, 95%CI 0.86 to1.15, P = 0.85 for GG vs. AA). In the subgroup analysis by the source of controls, no significant association was found either among hospital-based group (OR = 1.16, 95%CI 0.78 to 1.73) or population-based group (OR = 1.06, 95%CI 0.74 to 1.35). However, when stratified by cancer types, we found a significant association between the polymorphism with colorectal cancer (OR = 1.56, 95%CI 1.01 to 2.40 for GG vs. AA). CONCLUSION miR-27a rs895819 polymorphism was associated with increased risk of colorectal cancer in Chinese population.
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Affiliation(s)
- Lu Yuan
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, China
| | - Ting-ting Zhang
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, China
| | - Yan Ren
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, China
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Zhang X, Dong H, Tian Y. miRNA Biology in Pathological Processes. SPRINGERBRIEFS IN MOLECULAR SCIENCE 2015. [DOI: 10.1007/978-3-662-47293-4_2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Yan YX, Wu LJ, Zhang J, Wang S, Wang W, Dong J, He Y. Let-7 related genetic variation and risk of metabolic syndrome in a Chinese population. Endocr J 2015; 62:887-96. [PMID: 26178671 DOI: 10.1507/endocrj.ej15-0236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
MicroRNA (miRNA) related genetic variation may change miRNA binding affinity and mRNA expression levels of the target genes, thus leading to altered metabolic parameters. This study explored the influence of let-7 related single nucleotide polymorphisms (SNPs) on individual susceptibility to metabolic syndrome (MetS) in a Chinese population. Seven SNPs located at the pri-let-7 gene region, pre-let-7 gene region or 3'-UTR of the KRAS gene were selected. The SNPs were genotyped in 503 MetS patients and 529 normal controls using the high-throughput Sequenom genotyping platform. Unconditional logistic regression analysis was utilized to estimate the association between these SNPs and the risk of MetS. There are three SNPs significantly associated with MetS. The A allele of rs17276588 was associated with an increased risk effect for MetS (Adjusted OR=1.75, 95%CI 1.37-2.25, P<0.001). Rs10993081 AG genotype was significantly associated with an increased risk of MetS compared with AA genotypes (Adjusted OR=1.42, 95%CI 1.11-1.83, P=0.006). Rs10877887 TC genotype was significantly associated with an increased risk of MetS compared with TT genotypes (Adjusted OR=1.52, 95% CI 1.16-1.99, P=0.002). Additionally, interactions between rs7045890 and rs712, rs17276588 and rs10877887 were significantly associated with risk of MetS. In conclusion, our study found that let-7 related genetic variation is associated with MetS and may contribute to the susceptibility of MetS. Larger, prospective studies are warranted to validate our findings.
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Affiliation(s)
- Yu-Xiang Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
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Xu Q, Dong Q, He C, Liu W, Sun L, Liu J, Xing C, Li X, Wang B, Yuan Y. A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression. PLoS One 2014; 9:e95249. [PMID: 24760009 PMCID: PMC3997364 DOI: 10.1371/journal.pone.0095249] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Accepted: 03/24/2014] [Indexed: 02/07/2023] Open
Abstract
Background Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). Conclusions pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.
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Affiliation(s)
- Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Qiguan Dong
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Caiyun He
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Wenjing Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Liping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Jingwei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Chengzhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
| | - Xiaohang Li
- Gastrointestinal Surgery and Department 4 of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bengang Wang
- Hepatobiliary Surgery and Department 1 of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China
- * E-mail:
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Kawahara Y. Human diseases caused by germline and somatic abnormalities in microRNA and microRNA-related genes. Congenit Anom (Kyoto) 2014; 54:12-21. [PMID: 24330020 DOI: 10.1111/cga.12043] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 11/29/2013] [Indexed: 12/12/2022]
Abstract
The human genome harbors approximately 2000 genes that encode microRNAs (miRNAs), small non-coding RNAs of approximately 20-22 nt that mediate post-transcriptional gene silencing. MiRNAs are generated from long transcripts through stepwise processing by the Drosha/DGCR8, Exportin-5/RanGTP and Dicer/TRBP complexes. Given that the expression of each individual miRNA is tightly regulated, the altered expression of certain miRNAs plays a pivotal role in human diseases. For instance, germline and somatic mutations in the genes encoding the miRNA processing machinery have been reported in different cancers. Furthermore, certain miRNA genes are encoded within regions that are deleted or duplicated in individuals with chromosomal abnormalities, and the fact that the knockout of these miRNAs in animal models results in lethality or the abnormal development of certain tissues indicates that these miRNA genes contribute to the disease phenotypes. It has also been reported that mutations in miRNA genes or in miRNA-binding sites, which result in the impairment of tight regulation of target mRNA expression, cause human genetic diseases, although these cases are rare. This is in contrast to the aberrant expression of certain miRNAs that results from the impairment of transcriptional or post-transcriptional regulation, which has been reported frequently in various human diseases. The present review focuses on human diseases caused by mutations in genes encoding miRNAs and the miRNA processing machinery as well as in miRNA-binding sites. Furthermore, human diseases caused by chromosomal abnormalities that involve the deletion or duplication of regions harboring genes that encode miRNAs or the miRNA processing machinery are also introduced.
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Affiliation(s)
- Yukio Kawahara
- Laboratory of RNA Function, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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Iudicibus SD, Lucafò M, Martelossi S, Pierobon C, Ventura A, Decorti G. MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases. World J Gastroenterol 2013; 19:7947-7954. [PMID: 24307788 PMCID: PMC3848142 DOI: 10.3748/wjg.v19.i44.7947] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/16/2013] [Accepted: 10/19/2013] [Indexed: 02/06/2023] Open
Abstract
In spite of the introduction in therapy of highly effective biological agents, glucocorticoids (GCs) are still employed to induce remission in moderate to severe inflammatory bowel diseases (IBD), but considerable inter-individual differences in their efficacy and side effects have been reported. The effectiveness of these drugs is indeed very variable and side effects, particularly severe in pediatric patients, are common and often unpredictable: the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability. In this context, microRNAs (miRNAs) represent a new and promising field of research. miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level, and are fine-tuning regulators of diverse biological processes, including the development and function of the immune system, apoptosis, metabolism and inflammation. Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases, such as IBD. There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response; however, the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study. The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis, represents an important innovative approach that could be translated into clinical practice. In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs, and their potential role as molecular markers useful for predicting in advance GC response.
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