Association of a genetic variant in angiopoietin‐like 3 with serum HDL‐C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-04-18 DOI:10.1002/mgg3.2418

Malihe Aghasizadeh, Asieh Ahmadi Hoseini, Reza Sahebi, Tooba Kazemi, Parisa Asadiyan‐Sohan, Habibollah Esmaily, Sara Samadi, Amir Avan, Gordon A. Ferns, Saeede Khosravi, Hamideh Ghazizadeh, Ebrahim Miri‐Moghaddam, Majid Ghayour‐Mobarhan

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引用次数: 0

Abstract

BackgroundLoss‐of‐function (LOF) variants of the angiopoietin‐like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high‐density lipoprotein cholesterol (HDL‐C) concentrations and thereby affect the risk of cardiovascular disease (CVD).ObjectiveIn the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad‐Stroke and Heart‐Atherosclerotic‐Disorders (MASHAD) cohort.MethodsOne thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow‐up. After a 12‐h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra‐ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20.ResultsIndividuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01–2.02, p = 0.041). There was a 1.3‐fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non‐carriers (OR = 1.32, 95%CI = 1.06–1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL‐C.ConclusionWe have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

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血管生成素样 3 基因变异与血清高密度脂蛋白胆固醇和心血管疾病风险的关系：对 MASHAD 队列进行的一项为期 6 年的研究

背景据报道，血管生成素样 3（ANGPTL3）基因的功能缺失（LOF）变异与血清甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）的浓度有关，从而影响心血管疾病（CVD）的风险。本研究探讨了 ANGPTL 3 基因位点中的 rs10789117 与 Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) 队列中心血管疾病风险的关系。研究人员在一夜禁食 12 小时后采集 20 mL 血液样本，用于测量空腹血糖和血脂。提取 DNA 后，使用 Tetra-ARMS PCR（扩增难治性突变系统）对 ANGPTL3 基因中的 rs10789117 进行基因分型。采用χ2检验估计ANGPTL3基因中rs10789117变异的基因型频率。结果发现，与 AA 基因型相比，具有 AC/CC 基因型（rs10789117）的个体发生心血管疾病的风险更高（OR = 1.43，95%CI = 1.01-2.02，p = 0.041）。与非携带者相比，rs10789117 变异的 C 等位基因携带者发生心血管事件的风险增加了 1.3 倍（OR = 1.32，95%CI = 1.06-1.72，p 值 = 0.038）。在对照组中，不同基因型的血清甘油三酯水平存在明显差异，但在心血管疾病组中，这种差异并不明显。结论我们发现，ANGPTL3 基因多态性中的 rs10789117 C>A 与心血管疾病事件有关，这可能是伊朗人群心血管疾病风险分层的一个重要生物标志物。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.