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The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.

ABSTRACT: MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls). Our results indicated a higher prevalence of the miR-146a gene SNP rs2910164 C allele and CC genotype in patients with severe sepsis (rs2910164G versus rs2910164C: P = 0.0029, odds ratio (OR) = 1.664; GG+GC versus CC: P = 0.0045, OR = 1.947). Neither the genotype nor the allele in rs57095329 showed significant differences between the septic cases and the controls (P = 0.5901 and 0.3580, resp.), and no significant difference was observed in the subgroups. In addition, we confirmed that the two SNPs rs2910164 and rs57095329 could functionally affect the miR-146a expression levels and the reduction of miR146a was accompanied with the upregulation of the expression levels of TRAF-6 and IRAK-1 in severe sepsis patients. This present study might provide valuable clinical evidence that miR-146a gene polymorphism rs2910164 is associated with the risk of severe sepsis.

SUBMITTER: Shao Y

PROVIDER: S-EPMC3950573 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.

Shao Yiming Y Li Jia J Cai Yujie Y Xie Yuliu Y Ma Guoda G Li You Y Chen Yanyan Y Liu Gen G Zhao Bin B Cui Lili L Li Keshen K

Mediators of inflammation 20140220

MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095 ...[more]

PMID: 24701036

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Project description:BackgroundPolymorphisms of microRNA (miRNA), as a novel mechanism, are closely associated with disease states by interfering with miRNA function. Direct correlations have been identified between single-nucleotide polymorphisms (SNPs) in miRNA, but the effect on type 2 diabetes mellitus (T2DM) onset among Chinese population remains unclear. Therefore, the aim of this study was to identify correlations between common SNPs in miR-27a, miR-146a, and miR-124a with T2DM among a Chinese population, as well as to explore diabetic pathological mechanisms and the impact of environmental factors.MethodsSNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 controls. Logistic regression analysis was performed to compare mutation frequencies between cases and controls.ResultsWe found no significant correlations between all genotypes of these miRNAs and T2DM in our research. However, stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects (age < 45 years) (adjusted P = 0.043; odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.54-0.99). Furthermore, the rs895819CC genotype in overweight people (24 ≤ body mass index [BMI] < 28) was significantly associated with an increased risk of T2DM (adjusted P = 0.042; OR = 1.73; 95% CI = 1.02-2.94), while the rs2910164 genotype in miR-146a was not significantly correlated with T2DM. The genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol (adjusted P = 0.021).ConclusionsThe rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects (age < 45 years), while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects (24 ≤ BMI < 28 kg/m 2 ). The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene function. Thus, miRNA mimics or inhibitors that directly regulate miRNA expression present novel and promising therapeutic targets.

Project description:BACKGROUND:CD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population. METHODS:Three single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis. RESULTS:After adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR?=?1.368, 95%CI?=?1.070-1.749, P?=?0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR?=?1.397, 95%CI?=?1.078-1.809, P?=?0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR?=?1.337, 95%CI?=?1.069-1.673, P?=?0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR?=?1.351, 95%CI?=?1.060-1.702, P?=?0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P?>?0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P?=?0.029, P?=?0.047 and P<0.001, respectively). CONCLUSIONS:In conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations.

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The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.

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The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.

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