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Abstract
Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population.
Highlights
Coronary artery disease (CAD) accounts for roughly one half of all cardiovascular deaths and is a major cause of morbidity and mortality around the world
APOAI-CIII-AIV gene cluster polymorphisms that we aimed to study, i.e. Apo AI-75G > A polymorphism, Apo CIII- SstI polymorphism and Apolipoprotein A-IV (Apo AIV)-Thr347Ser polymorphism are among the important ones and studies of these loci among Indians populations are limited (Singh, Singh, Gaur, & Kaur, 2007; Singh, Singh, Kaur, & Grewal, 2008)
No significant difference was observed for dietary habits, though patient group reported a higher number of non-vegetarians (46 vs. 39%, p = 0.19, NS)
Summary
Coronary artery disease (CAD) accounts for roughly one half of all cardiovascular deaths and is a major cause of morbidity and mortality around the world. Both genetic and environmental factors play a crucial role in the causation of CAD. The lipid abnormalities significantly contribute to the risk of developing premature CAD. One of the commonly studied lipid gene cluster is the Apolipoprotein (Apo) AICIII-AIV gene cluster (Agrawal & Mastana, 2014). This group of genes is located on chromosome 11q23–q24. Several polymorphic forms of the genes in this cluster can alter plasma levels of various lipids but can affect expression of other genes and/or modulate the action of different proteins within the human body, which can lead to higher chance of developing premature CAD
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