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在涉及脂质代谢的 ZNF259 基因的遗传多态性与冠状动脉疾病之间存在关联。

There is an association between a genetic polymorphism in the ZNF259 gene involved in lipid metabolism and coronary artery disease.

机构信息

Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Gene. 2019 Jul 1;704:80-85. doi: 10.1016/j.gene.2019.02.101. Epub 2019 Mar 19.

Abstract

BACKGROUND

Recent genome-wide association studies (GWAS) have identified several genetic variants that influence the risk of dyslipidemia and coronary artery disease (CAD). In this study, we have examined the potential association of five SNPs variants related to lipid pathway, previously identified in GWAS studies (ZNF259 C>G, CETP I405VA/G, LPA C>T, LPLS447X and PSRC1 A>G) with CAD.

METHODS

Two hundred and ninety subjects including 194 patients with coronary artery disease and 96 controls were enrolled, followed by the analyses of anthropometric/biochemical parameters. Genotyping was carried out using Taq-Man real-time PCR based method. The association of the genetic polymorphisms with CAD was determined using univariate and multivariate analyses.

RESULTS

CAD patients had a higher (p < 0.05) fasting blood glucose (FBG), total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C) and waist circumference. Results showed that subjects with CETP rs5882 genetic variant, AA&AG genotypes, had a higher risk of developing Coronary artery disease [OR: 2.1, 95% CI (1.2-4.1), p value = 0.015]. Also subjects who carried the G allele of the ZNF259 polymorphism were at an increased the risk of developing CAD [OR 1.86, 95% CI: 1.06-3.25, p value = 0.029] and had an increased TC, LDL and TG levels (p < 0.05). Furthermore, no statistically significant association was found between genetic polymorphisms of PSRC1 A>G, LPL S447X and LPA C>T and CAD.

CONCLUSION

We identified a relationship between a genetic variant in CETP and ZNF259 gene with CAD and CAD and lipid profile, respectively. Further investigation in a larger population may help to investigate the value of emerging marker as a risk stratification marker in CAD and its risk factors.

摘要

背景

最近的全基因组关联研究(GWAS)已经确定了一些影响血脂异常和冠心病(CAD)风险的遗传变异。在这项研究中,我们研究了之前在 GWAS 研究中确定的与脂质通路相关的五个 SNP 变异(ZNF259 C>G、CETP I405VA/G、LPA C>T、LPLS447X 和 PSRC1 A>G)与 CAD 的潜在关联。

方法

共纳入 290 例受试者,包括 194 例 CAD 患者和 96 例对照,随后分析了人体测量/生化参数。采用 Taq-Man 实时 PCR 方法进行基因分型。采用单因素和多因素分析方法确定遗传多态性与 CAD 的关系。

结果

CAD 患者空腹血糖(FBG)、总胆固醇(TC)、高敏 C 反应蛋白(hs-CRP)、低密度脂蛋白胆固醇(LDL-C)和腰围较高(p<0.05)。结果显示,CETP rs5882 基因变异 AA&AG 基因型的受试者发生冠心病的风险更高[OR:2.1,95%CI(1.2-4.1),p 值=0.015]。携带 ZNF259 多态性 G 等位基因的受试者患 CAD 的风险也增加[OR 1.86,95%CI:1.06-3.25,p 值=0.029],TC、LDL 和 TG 水平升高(p<0.05)。此外,PSRC1 A>G、LPL S447X 和 LPA C>T 基因多态性与 CAD 之间无统计学显著相关性。

结论

我们确定了 CETP 和 ZNF259 基因中的遗传变异与 CAD 之间以及 CAD 与脂质谱之间的关系。在更大的人群中进行进一步研究可能有助于研究新兴标志物作为 CAD 及其危险因素的风险分层标志物的价值。

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