Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population

Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population
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DOI:
10.1038/jhg.2010.54
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发表时间:
2010-08-01
影响因子:
3.5
通讯作者:
Mittal, Balraj
Mittal, Balraj
中科院分区:
生物学3区
文献类型:
--
作者:
Srivastava, Kshitij;Srivastava, Anvesha;Mittal, Balraj

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microRNA(miRNAs)是一种小的非编码RNA分子,其功能是基因表达的负调节因子。miRNA基因中常见的遗传变异(单核苷酸多态性,SNP)可能会改变它们的表达或成熟,导致不同的功能后果。目前的病例对照研究评估了前体miRNA中的三个SNP(rs 2910164,rs 11614913和rs3746444)与北印度人群中230例胆囊癌(GBC)病例和230例对照中胆囊癌(GBC)风险的潜在关联。计算单个SNP与GBC相互作用的比值比(OR)和95%置信区间(95%CI)。在rs 2910164、rs 11614913和rs3746444变异基因型携带者之间观察到风险无显著增加(OR分别为1.3、1.3和1.1)。这种增加的风险在GBC胆结石患者中更为显著(OR分别为1.4、1.6和1.1)。为了进一步评估变异等位基因的累积效应,我们进行了联合不利基因型分析,其显示了临界统计学显著性。与低风险组(0-2个变异等位基因)相比,高风险组(>2个变异等位基因)的GBC风险增加1.7倍(95%CI =1.0-2.8)(P(趋势)=0.056)。这些发现首次表明,常见的miRNA变异可能不会导致北印度人群的GBC易感性。Journal of Human Genetics(2010)55,495-499; doi:10.1038/jhg.2010.54; 2010年6月3日在线发表
MicroRNAs (miRNAs) are small, non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Present case-control study evaluated the potential association of three SNPs (rs2910164, rs11614913 and rs3746444) in pre-miRNAs with gallbladder cancer (GBC) risk in 230 GBC cases and 230 controls in a North Indian population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for the association of individual SNPs and their interactions with GBC. A non-significant increased risk was observed between carriers of variant genotypes of rs2910164, rs11614913 and rs3746444 (ORs=1.3, 1.3 and 1.1, respectively). This increased risk was more profound in GBC patients with gallstones (ORs=1.4, 1.6 and 1.1, respectively). To further evaluate the cumulative effects of the variant allele, we did a combined unfavorable genotype analysis, which showed a borderline statistical significance. In comparison with the low-risk group (0-2 variant alleles), the high-risk group (>2 variant alleles) had a 1.7-fold (95% CI=1.0-2.8) increased risk for GBC (P(trend)=0.056). These findings suggest, for the first time, that common miRNA variants may not contribute to GBC susceptibility in North Indian population. Journal of Human Genetics (2010) 55, 495-499; doi:10.1038/jhg.2010.54; published online 3 June 2010