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评估与冠状动脉疾病患者中ATP结合盒转运体A1(ABCA1)基因相关的基因多态性以及血清脂质谱水平的波动情况。

Assessment of genetic polymorphism associated with ATP-binding cassette transporter A1 (ABCA1) gene and fluctuations in serum lipid profile levels in patients with coronary artery disease.

作者信息

Bogari Neda M, Babalghith Ahmad O, Bouazzaoui Abdellatif, Aljohani Ashwag, Dannoun Anas, Elkhateeb Osama, Amin Amr A, Bogari Mazin K, Mazhar Abdulbari A, Porqueddu Massimo, Khan Imran Ali

机构信息

Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 715, Makkah 21955, Saudi Arabia.

Science and Technology Unit, Umm Al Qura University, P.O. Box 715, Makkah 21955, Saudi Arabia.

出版信息

Saudi Pharm J. 2021 Dec;29(12):1458-1465. doi: 10.1016/j.jsps.2021.11.007. Epub 2021 Nov 15.

Abstract

BACKGROUND

Coronary artery disease (CAD) is one of the common genetic and clinical risk factors associated with cardiovascular and multifactorial disorder. ATP-binding cassette transporter A1 (ABCA1) gene plays an important role in lipid metabolism and in multiple studies associated with CAD. However, more studies are needed to identify the exact role of single nucleotide polymorphisms which may cause CAD.

OBJECTIVES

The aim of this study is to investigate the genetic association of polymorphism g.1051G > A in the gene with CAD patients in the Saudi population.

METHODS

We included 315 confirmed CAD cases, and 205 non-CAD or control subjects in this case-control study. DNA isolation was carried out for all registered participants and the polymorphism g.1051G > A was genotyped with Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism analysis with EcoNI restriction enzyme.

RESULTS

Modifiable risk factors such as Body Mass Index, smoking and diabetes were strongly associated and non-modifiable risk factors such as hypertension (Systolic Blood Pressure and Diastolic Blood Pressure) and serum analysis such as Fasting Blood Glucose, Total cholesterol (TC), Triglyceride (TG) and LDL-c were significantly associated in CAD cases (p < 0.05). Allele (OR-1.73;95% CI:1.33-2.26; p = 0.0004), GA vs GG (OR-2.26; 95% CI: 1.53-3.35; p = 0.0003 and dominant inheritance pattern (OR-2.23; 95% CI:1.56-3.20; p = 0.00009 was strongly associated with CAD cases and control subjects. The frequency level of use of atorvastatin was significantly different among GG, GA and AA subjects. Additionally, TC and TG levels were influenced by the presence of g.1051G > A polymorphism.

CONCLUSION

The polymorphism g.1051G > A in the gene is closely associated with the existence of the CAD subjects. This polymorphism could also affect the serum levels of the lipid profile, suggesting a possible occurrence of CAD in the Saudi population.

摘要

背景

冠状动脉疾病(CAD)是与心血管及多因素疾病相关的常见遗传和临床风险因素之一。ATP结合盒转运蛋白A1(ABCA1)基因在脂质代谢中起重要作用,且在多项与CAD相关的研究中有所涉及。然而,需要更多研究来确定可能导致CAD的单核苷酸多态性的确切作用。

目的

本研究旨在调查沙特人群中该基因g.1051G>A多态性与CAD患者的遗传关联。

方法

在这项病例对照研究中,我们纳入了315例确诊的CAD病例和205例非CAD或对照受试者。对所有登记参与者进行DNA提取,并采用聚合酶链反应对g.1051G>A多态性进行基因分型,随后用EcoNI限制性内切酶进行限制性片段长度多态性分析。

结果

可改变的风险因素如体重指数、吸烟和糖尿病与CAD密切相关,不可改变的风险因素如高血压(收缩压和舒张压)以及血清分析指标如空腹血糖、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇在CAD病例中显著相关(p<0.05)。等位基因(OR-1.73;95%CI:1.33-2.26;p=0.0004)、GA与GG(OR-2.26;95%CI:1.53-3.35;p=0.0003)以及显性遗传模式(OR-2.23;95%CI:1.56-3.20;p=0.00009)与CAD病例和对照受试者密切相关。阿托伐他汀的使用频率水平在GG、GA和AA受试者之间存在显著差异。此外,TC和TG水平受g.1051G>A多态性的影响。

结论

该基因中的g.1051G>A多态性与CAD受试者的存在密切相关。这种多态性还可能影响血脂水平,提示沙特人群中可能存在CAD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fc/8720826/5e6f2a334d45/gr1.jpg

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