Analyzing the role of genetic variants in microRNAs and its role as a modulator towards Chronic Obstructive Pulmonary disease (COPD) susceptibility in North Indian population

IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY
Gene Pub Date : 2025-03-10 DOI:10.1016/j.gene.2025.149413
Anmol Bhatia , Atul Kumar Upadhyay , Kranti Garg , Vishal Chopra , Siddharth Sharma
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Abstract

Background

miRNAs can target numerous genes, with slight expression changes potentially leading to significant alterations in protein-coding gene expression, affecting various biological processes and possibly worsening conditions like COPD.

Objectives

This study examines the link between six miRNA SNPs (MIR605, MIR608, MIR3117, MIR149, MIR499, and MIR25) and COPD risk in a North Indian population and the functional impact of these miRNA-SNPs on COPD-related pathological factors.

Materials and Methods

To assess genotypes, a case-control study was conducted with 323 COPD cases and 350 hospital controls. Logistic regression determined the odds ratio and 95% confidence interval for the SNP-COPD association, with stratified analysis for clinical parameters, symptoms, and risk factors. SNP-SNP interactions were analyzed using combinatorial analysis, MDR, and CART analysis.

Results

MIR25 SNP rs1527423 and MIR608 SNP rs4919510 were significantly associated with COPD risk (OR = 6.38; p < 0.0001 and OR = 1.43, p = 0.02, respectively). rs1527423 remained significant in stratified analysis for age (OR = 6.19; pc = 0.0005), gender (males; OR = 5.93; pc < 0.0001), and smoking status (smokers; OR = 5.02; pc = 0.0006). rs4919510 was associated with COPD risk in patients aged ≥ 65 years (OR = 2.38, pc = 0.0054). MIR605 SNP rs2043556 had a protective effect in non-smokers (OR = 0.142; pc = 0.048). MIR3117 SNP rs4655646 was linked to COPD symptoms. Doublet combinations of each SNP with rs1527423 increased COPD risk. CART analysis identified rs1527423 as a critical factor, with the genotypic combination of 149(M)-3117(M; W)-605(M; W)-608(M; H)-25(W) showing the highest COPD risk (OR = 11; p = 0.0445).

Conclusions

The study suggests MIR25 SNP rs1527423 as a risk factor for COPD in North Indian populations.
分析microrna遗传变异的作用及其在北印度人群中作为慢性阻塞性肺疾病(COPD)易感性调节剂的作用
mirna可以靶向许多基因,轻微的表达变化可能导致蛋白质编码基因表达的显著改变,影响各种生物过程,并可能恶化COPD等疾病。本研究探讨了北印度人群中6种miRNA snp (MIR605、MIR608、MIR3117、MIR149、MIR499和MIR25)与COPD风险之间的联系,以及这些miRNA snp对COPD相关病理因素的功能影响。为了评估基因型,我们对323例COPD患者和350名医院对照进行了病例-对照研究。通过对临床参数、症状和危险因素的分层分析,Logistic回归确定SNP-COPD相关性的优势比和95%置信区间。采用组合分析、MDR和CART分析分析SNP-SNP相互作用。结果smir25 SNP rs1527423和MIR608 SNP rs4919510与COPD风险显著相关(OR = 6.38;p & lt;0.0001和OR = 1.43, p = 0.02)。rs1527423在年龄分层分析中仍然显著(OR = 6.19;Pc = 0.0005),性别(男性;或= 5.93;pc & lt;0.0001),吸烟状况(吸烟者;或= 5.02;pc = 0.0006)。rs4919510与≥65岁患者COPD风险相关(OR = 2.38, pc = 0.0054)。MIR605 SNP rs2043556对非吸烟者有保护作用(OR = 0.142;pc = 0.048)。MIR3117 SNP rs4655646与COPD症状有关。每个SNP与rs1527423的双重组合增加了COPD的风险。CART分析发现rs1527423为关键因子,基因型组合为149(M)-3117(M);-605 W) (M;-608 W) (M;H)-25(W)显示COPD风险最高(OR = 11;p = 0.0445)。该研究提示MIR25 SNP rs1527423是北印度人群COPD的危险因素。
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来源期刊
Gene
Gene 生物-遗传学
CiteScore
6.10
自引率
2.90%
发文量
718
审稿时长
42 days
期刊介绍: Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.
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