Association of APOC3 and PNPLA3 genetic polymorphism in adult Pakistani population with non-alcoholic fatty liver disease

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene Pub Date : 2025-07-23 DOI:10.1016/j.humgen.2025.201453

Muhammad Masroor , Zeba Haque , Haya Anwar , Farina Hanif , Waqas Ahmed Farooqui

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Abstract

Background

NAFLD occurs in many individuals without obesity, metabolic syndrome, or diabetes, indicating other factors like genetic predisposition play a significant role.

Objective

This study investigates the association between genetic polymorphisms (PNPLA3 and APOC3) and metabolic markers, including liver enzymes and HbA1c, in predicting NAFLD within a Pakistani population.

Methods

This case-control study was conducted at Dow University of Health Sciences from 2015 to 2021. This reports part of the data from a larger project exploring risk factors for NAFLD. Data from 60 participants including gender and age matched 43 NAFLD cases and 17 controls were analyzed for genetic polymorphisms (PNPLA3 rs738408, rs738409; APOC3 rs2845116, rs2845117) with power estimates ranging from 71.6 to 90 % for genetic parameters. Anthropometric, biochemical, and liver enzyme measurements and DNA sequencing were performed. Categorical variables were analyzed using chi-square or Fisher's exact tests, for continuous variables independent t-tests (normally distributed) and Mann-Whitney U tests for non-normal liver parameters were applied. Genetic associations were evaluated through chi-square tests with Monte Carlo simulation (for small cell counts) and effect sizes calculated using Cramer's V.

Results

Significant associations were found between NAFLD and polymorphisms APOC3 rs2845117 (C allele, p = 0.027 and APOC3 rs2845116 (T allele, p = 0.039). A significant association was also observed for PNPLA3 10109C > G (p = 0.00.030) but not PNPLA3 rs738408; 10,112C > T (p = 0.073). Cases showed significantly higher BMI, HbA1c, fasting blood glucose, serum triglycerides, and liver enzymes (ALT, Alkaline phosphatase, Gamma GT) compared to controls (p < 0.05).

Conclusions

Metabolic and anthropometric factors were strongly associated with NAFLD. Genetic variants in APOC3 (rs2845117, rs2845116) and PNPLA3 (rs738409) but not rs738408 showed significant associations with NAFLD. APOC3 rs2845117 CC conferring the highest risk for NAFLD. These markers may aid early detection and guide targeted prevention.

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apo3和PNPLA3基因多态性与巴基斯坦成年非酒精性脂肪肝患者的关系

背景nafld发生在许多没有肥胖、代谢综合征或糖尿病的个体中，表明遗传易感性等其他因素也起着重要作用。目的本研究探讨遗传多态性（PNPLA3和APOC3）与代谢标志物（包括肝酶和HbA1c）在预测巴基斯坦人群NAFLD中的关系。方法2015 - 2021年在陶氏健康科学大学进行病例对照研究。本文报告的部分数据来自于一个探索NAFLD风险因素的大型项目。来自60名参与者（包括性别和年龄）的数据与43例NAFLD病例和17例对照组相匹配，分析遗传多态性(PNPLA3 rs738408, rs738409；APOC3 rs2845116, rs2845117)，遗传参数的功率估计范围为71.6至90%。进行人体测量、生化、肝酶测定和DNA测序。分类变量分析采用卡方检验或Fisher精确检验，连续变量分析采用独立t检验（正态分布），非正常肝脏参数分析采用Mann-Whitney U检验。通过蒙特卡罗模拟卡方检验评估遗传关联（小细胞计数），并使用Cramer's v计算效应量。结果发现NAFLD与APOC3 rs2845117 （C等位基因，p = 0.027）和APOC3 rs2845116 （T等位基因，p = 0.039）多态性之间存在显著关联。PNPLA3 10109C >；G (p = 0.00.030)，但PNPLA3 rs738408不存在；10112 c比;p = 0.073)。与对照组相比，这些病例的BMI、HbA1c、空腹血糖、血清甘油三酯和肝酶（ALT、碱性磷酸酶、γ GT）均显著升高(p <；0.05)。结论代谢和人体测量因素与NAFLD密切相关。APOC3基因变异（rs2845117、rs2845116）和PNPLA3基因变异（rs738409）与NAFLD存在显著相关性，但rs738408基因变异不存在。APOC3 rs2845117 CC具有NAFLD的最高风险。这些标记可能有助于早期发现和指导有针对性的预防。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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