ASSOCIATION OF THE APOLIPOPROTEIN A-I GENE POLYMORPHISMS WITH CARDIOVASCULAR DISEASE RISK FACTORS AND ATHEROGENIC INDICES IN PATIENTS FROM ASSAM, NORTHEAST INDIA
Bora K1,2,*, Pathak MS2, Borah P3, Hussain Md.I.3, Das D4
*Corresponding Author: : Dr. Kaustubh Bora, Regional Medical Research Centre, Northeast Region, Indian Council of Medical Research (ICMR), P.O. Box 105, Dibrugarh-786001, Assam, India. Tel: +91-943-557-2062. Fax: +91-364-253-8003. E-mail: kaustubhbora1@gmail.com
page: 59

INTRODUCTION

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. In 2012, an estimated 17.5 million people died of CVDs, representing about 31.0% of all global deaths [1]. Atherosclerosis, which refers to the progressive hardening of arteries and narrowing of lumen due to fibro-fatty changes in the vessel wall, is the major pathophysiological process underlying CVDs [2]. The risk factors for atherosclerosis and CVDs are many, such as altered serum lipid levels (also called dyslipidemia), smoking, alcohol, obesity, male gender, advancing age, ethnicity and genetic predisposition, diabetes and hypertension [1-3]. The apolipoprotein A1 gene (APOA1), which is a part of the APOA1-CIII-AIV gene cluster on chromosome 11, is a major site controlling the expression of lipids and lipoproteins [4-7]. Thus, allelic variants of APOA1 that influence CVD risk are of interest. The role of two single nucleotide polymorphisms (SNPs), located in the regulatory regions of APOA1, namely G75A and C+83T, is being increasingly appreciated in this regard. These SNPs have been implicated in various clinical conditions [8-11], but most notably with reference to CVDs and their risk factors [12-18]. The G-75A site lies in the promoter region, while the C+83T site lies in the first intron of APOA1 [19,20]. These polymorphic sites are also cleavage sites for the restriction endonuclease, MspI and thus are amenable to detection by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) [15,16,21]. These SNPs are thought to influence several quantitative traits that are risk factors for CVD, such as: serum lipids [viz. total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG)], indices of obesity [viz. waist circumference (WC) and body mass index (BMI)], and blood pressure (BP) [12-19]. Recently, the G-75A and C+83T polymorphisms were described in the native population of Assam, where significant differences were noted in their distribution as compared to populations of neighboring regions [21]. Assam is the most populated state in northeast India, an ethnically distinct region that is often regarded as the ethnological transition zone between the Indian subcontinent and east/ southeast Asia. Decreased level of HDL-C is a major risk factor for CVD [1-3] and a common form of dyslipidemia in Assam [22,23]. Moreover, APOA1 codes for the major part of the proteome of HDL particles [19]. Assam also has a sizeable burden of many other conditions (high BP, diabetes, schizophrenia, increased TG, etc.) where APOA1 is implicated [23-26]. Thus, it is of interest to investigate whether the G-75A and C+83T polymorphisms have a role to play in relation to these conditions in the population of Assam. On this basis, we decided to conduct a pilot study to explore if G-75A and C+83T SNPs of APOA1 were associated with cardiovascular risk factors in the population of Assam. Our primary objective was to determine whether G-75A and C+83T polymorphisms were associated with decreased HDL-C. Our secondary objective was to assess if these polymorphisms were associated with other CVD risk factors, viz. lipid fractions (TC, LDL-C, VLDL-C, TG); obesity indices (WC and BMI); and BP (systolic and diastolic). Additionally, we studied the associations of these SNPs with several atherogenic indices [also known as lipid ratios, namely: Castelliís Risk Index-I (CRI-I), Castelliís Risk Index-II (CRI-II), atherogenic index of plasma (AIP), atherogenic coefficient (AC), non-HDL cholesterol fraction (non-HDL-C)]. Atherogenic indices reflect the propensity of the serum lipids to induce atherosclerotic changes. They are increasingly recognized as valuable predictors of CVD risk [27-29], often better than the traditional lipid measures, but genetic factors influencing them have been scarcely investigated.



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