Evaluation of the association between the PNPLA3 rs738409 variants with the incidence of atherosclerosis in patients with different fatty liver grades

IF 0.9 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2025-03-01 Epub Date: 2025-02-07 DOI:10.1016/j.genrep.2025.102160

Shaimaa Mohamed , Ghada M. Salum , Reham Ibrahim Siddik , Sherif Hassan Elwan , Ahmed Ibrahim Saleh , Hamdi Sweilam , Reham M. Dawood

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Abstract

Background

The role of PNPLA3 gene is pivotal in lipid droplet remodeling, VLDL secretion, contributing to the development of NAFLD. The data obtained from GWAS approach reported the importance of PNPLA3 gene polymorphism as a key factor on influencing the NAFLD susceptibility among different ethnicities. PNPLA3 rs738409 risk allele G is hypothesized to be linked with high levels of soluble intercellular adhesion molecule 1 (sICAM-1) which promotes leukocyte adhesion ending with atherosclerosis. The current study aims to investigate the association between the PNPLA3 rs738409 variant in a cohort of NAFLD patients' concomitant with atherosclerosis.

One hundred NAFLD patients and fifty healthy individuals have been recruited. The atherosclerosis was assessed by Carotid Doppler. The PNPLA3 (rs738409 C > G) polymorphism is genotyped by using TaqMan probe assay.

Results

Despite the lack of statistical significance, the CG carriers of PNPLA3 had an increased risk of having NAFLD (1.8 folds) when compared to CC carriers. Additionally, by classifying patients based on atherosclerosis grades, a significant association was found between the GG risk genotype of PNPLA3 and advanced stages of atherosclerosis (p = 0.014).

Conclusions

This study highlights the link between risk allele (G) of PNPLA3 and the risk for having NAFLD, as well as the correlation with advanced atherosclerosis among Egyptian subjects. Also, our findings did not support a direct association between the histological severity of NAFLD and the progression of atherosclerosis stages.

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评估PNPLA3 rs738409变异与不同脂肪肝分级患者动脉粥样硬化发生率之间的关系

背景PNPLA3基因在脂滴重塑、VLDL分泌、NAFLD发生过程中起关键作用。GWAS方法获得的数据报道了PNPLA3基因多态性作为影响不同种族NAFLD易感性的关键因素的重要性。PNPLA3 rs738409风险等位基因G被假设与高水平的可溶性细胞间粘附分子1 （sICAM-1）有关，该分子可促进白细胞粘附，最终导致动脉粥样硬化。本研究旨在探讨PNPLA3 rs738409变异在NAFLD合并动脉粥样硬化患者队列中的相关性。招募了100名NAFLD患者和50名健康人。颈动脉多普勒检查动脉粥样硬化。PNPLA3 (rs738409 C >；G)多态性采用TaqMan探针法进行基因分型。结果PNPLA3基因CG携带者发生NAFLD的风险较CC携带者增加（1.8倍），但差异无统计学意义。此外，根据动脉粥样硬化等级对患者进行分类，发现PNPLA3的GG风险基因型与动脉粥样硬化晚期之间存在显著相关性（p = 0.014）。结论：本研究强调了PNPLA3风险等位基因(G)与NAFLD风险之间的联系，以及与埃及受试者中晚期动脉粥样硬化的相关性。此外，我们的研究结果不支持NAFLD的组织学严重程度与动脉粥样硬化阶段进展之间的直接关联。

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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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports 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. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.