Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster

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.

Keywords:

• apolipoprotein (Apo) AI-CIII-AIV gene cluster
• single nucleotide polymorphisms (SNPs)
• serum lipids
• coronary artery disease (CAD)
• linkage disequilibrium, haplotypes

Public Interest Statement

Our’s is the first report investigating association of polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster with serum lipids and coronary artery disease (CAD) in a single centre, well characterized sample of North Indians hailing from the state of Uttar Pradesh, India. CAD is attributed to nearly half of the deaths globally and Indians in general are more prone to early development of CAD. Genetic basis of CAD is still not completely understood. We, in the present study observed that individual and combination of Apo gene cluster polymorphisms tend to influence serum lipid levels which in turn may enhance risk of developing CAD amongst healthy controls. Though the odds for developing CAD in several comparisons were found to be above 1, individual loci did not achieve a statistical significance possibly due to small sample size of the study. Larger, multi-centric studies are warranted to confirm these associations.

Competing Interests

The authors declare no competing interests.

Funding

This work was supported by The Wellcome Trust Biomedical Vacation Scholarship.

Supplementary material

The supplementary material for this paper is available online at http://dx.doi.10.1080/2331205X.2016.1266789.

Additional information

Notes on contributors

Himanshu Rai

Himanshu Rai is a research scientist working in the field of heart disease who did collection and analysis of these samples.

Nakul Sinha

Nakul Sinha is Professor of Cardiology and did clinical evaluation and recruitment of participants.

James Finn

James Finn was an undergraduate student who carried out laboratory based genetic analyses which were supervised by Sarabjit Mastana, Senior Lecturer in Human Genetics, who planned and co-ordinated these analyses.

Suraksha Agrawal

Suraksha Agrawal is Professor of Medical Genetics and who planned and coordinated this research work. She has extensively published in medical and human genetics.