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常见的前 microRNA 基因变异与印度北部人群胆囊癌风险的相关性研究。

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

机构信息

Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

出版信息

J Hum Genet. 2010 Aug;55(8):495-9. doi: 10.1038/jhg.2010.54. Epub 2010 Jun 3.

Abstract

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.

摘要

微小 RNA(miRNA)是一种小的非编码 RNA 分子,作为基因表达的负调控因子。miRNA 基因中的常见遗传变异(单核苷酸多态性,SNP)可能改变其表达或成熟,从而导致不同的功能后果。本病例对照研究评估了三个 miRNA 前体中的 SNP(rs2910164、rs11614913 和 rs3746444)在 230 例印度北部人群的胆囊癌(GBC)病例和 230 例对照中的潜在关联。个体 SNP 及其与 GBC 的相互作用的比值比(OR)和 95%置信区间(95%CI)进行了计算。携带 rs2910164、rs11614913 和 rs3746444 变异基因型的个体的风险比(ORs)分别为 1.3、1.3 和 1.1。在有胆结石的 GBC 患者中,这种风险增加更为明显(ORs 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,我们进行了组合不利基因型分析,结果显示具有边缘统计学意义。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 风险增加了 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 变体可能不会导致印度北部人群的 GBC 易感性增加。

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