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      Common functional polymorphism within miR-146a and miR-196a-2 as susceptibility loci for hepatocellular carcinoma: An updated meta-analysis

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      1 , 1 , , , , *
      Meta Gene
      Elsevier
      HCC, MiRNA

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          Abstract

          Background

          Mutations or single nucleotide polymorphisms (SNPs) within the gene region of microRNAs play an important role for the development of hepatocellular carcinoma (HCC). Extensive studies have tried to investigate the susceptibility role of miR-146a rs2819164 and miR-196a-2 rs11614913. However, these results are still inconsistent and inconclusive. We undertook a meta-analysis containing primarily Asian studies to assess the associations of the two SNPs with HCC risk.

          Methods

          19 studies including miR-146a (7170 cases and 9443 controls) and 15 studies including miR-196a-2 (6417 cases and 7627 controls) were used for meta-analysis. Odds ratios and 95% CI were calculated to assess the association in five different genetic models.

          Results

          For the rs2910164 polymorphism of miR-146a, significantly increased risks for HCC were observed when all studies were pooled under two models (CG vs CC: OR = 1.11, 95% CI = 1.02–1.21, P = 0.021; GG + CG vs CC: OR = 1.11, 95% CI = 1.01–1.22, P = 0.035). For the rs11614913 polymorphism of miR-196a-2, significant increased risks for HCC development were observed when all studies were pooled under four models (C vs T: OR = 1.14, 95% CI = 1.06–1.23, P = 0.001; CC vs TT: OR = 1.31, 95% CI = 1.12–1.53, P = 0.001; CC + TC vs TT: OR = 1.16, 95% CI = 1.03–1.31, P = 0.018; CC vs TC + TT: OR = 1.14, 95% CI = 1.00–1.30, P = 0.043).

          Conclusion

          Our results show that the two common SNPs within the miRNAs were associated with modest increased risk of HCC (OR < 1.6), especially in the Asian population. Larger population-based studies validating these results are needed.

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          Most cited references33

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Genome-wide association studies for complex traits: consensus, uncertainty and challenges.

            The past year has witnessed substantial advances in understanding the genetic basis of many common phenotypes of biomedical importance. These advances have been the result of systematic, well-powered, genome-wide surveys exploring the relationships between common sequence variation and disease predisposition. This approach has revealed over 50 disease-susceptibility loci and has provided insights into the allelic architecture of multifactorial traits. At the same time, much has been learned about the successful prosecution of association studies on such a scale. This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
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              Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.

              To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).
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                Author and article information

                Contributors
                Journal
                Meta Gene
                Meta Gene
                Meta Gene
                Elsevier
                2214-5400
                15 November 2015
                February 2016
                15 November 2015
                : 7
                : 40-47
                Affiliations
                Department of Clinical Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China
                Author notes
                [* ]Corresponding author. xqyyjyk@ 123456aliyun.com
                [1]

                These authors contributed equally to this work.

                Article
                S2214-5400(15)00068-7
                10.1016/j.mgene.2015.11.002
                4707244
                26862480
                3cd0114a-842e-4b26-9711-862315f040ac
                © 2015 Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 June 2015
                : 29 October 2015
                : 14 November 2015
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                hcc,mirna
                hcc, mirna

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