A study of PON1 as a susceptibility gene for hyperlipidaemia and onset of coronary artery disease

Abstract

The involvement of paraoxonase 1 (PON1) gene polymorphism in hyperlipidaemia (HPLD) and early onset of coronary artery disease (CAD) remains poorly studied. In a preliminary genome‐wide linkage study of early onset CAD involving two families (22 individuals) with predominant familial hypercholesterolaemia, we identified several peaks, among others, on chromosome (chr) 7 which harbours the PON1 gene using the Affymetrix Gene Chip 250 sty1 mapping array. The present study pursued a population‐based association analysis for 6 selected SNPs rs854560 (1), rs662(3), rs854552 (3), rs3917577 (4) and rs3735590 (5) in the PON1 gene in 3048 individuals (1013 HLPD cases versus 2035 controls) using the Applied Biosystems real‐time PCR procedure. Two of the 6 variants, rs662 [Odds ratio(95% Confidence Interval = 1.13(1.01–1.26); p=0.031] and rs3917577[1.20(1.04–1.38); p=0.013], individually conferred risk for HLPD. While no association was found between any of these variants with CAD (1796 cases versus 1261 controls) per se, classifying the CAD patients as harbouring (n=748) or not harbouring HLPD (n=997) retained the significance of the rs3917577 as a causative factor [1.23(1.03–1.47); p=0.023] for CAD. In contrast, classifying the HPLD patients as having CAD or not, yielded no delineable relationship. On the other hand, the rs854552 was associated with resistance (p=0.007) to developing HPLD among the CAD individuals. No confounding effect of gender, age, MI, T2D, or obesity was observed on these relationships. The results indicate the PON1 gene is a susceptibility locus for HLPD, and harbouring of the rs3917577 variant increases the risk of acquiring CAD among hyperlipidaemic individuals.