APOA1-75 G to A Substitution Associated with Severe Forms of CAD, Lower Levels of HDL and apoA-I among Northern Indians

Abstract

Apolipoprotein A-I (APOA1 gene, apoA-I protein) is the major protein for plasma high density lipoprotein (HDL). The relationship of APOA1-75G/A polymorphism with lipid profile and coronary artery disease (CAD) is unclear. Out of 370 individuals initially recruited, 164 angiographically proven CAD patients (≥ 70% stenosis) and 36 individuals with normal coronaries or insignificant CAD (NCAD, ≤ 50% stenosis) from Delhi and adjoining areas were selected for analysis based on the set criteria. Polymorphism was determined by PCR followed by MspI restriction digestion. Lipid profile was estimated by enzymatic kit and apoA-I levels by immunoturbidimetry. A highly significant increasing trend in ‘A’ allele frequency was observed with the rise in severity of CAD: NCAD (0.097) < SVD (single vessel disease) (0.117) < DVD (double vessel disease) (0.223) < TVD (triple vessel disease) (0.291). In comparison to GG individuals, the OR of ‘A’ allele carriers to develop SVD, DVD, TVD was 1.3, 2.8 and 4.2 respectively (p_trend = 0.007). Analysis of intergenotypic variations in the lipid profile revealed significantly lower levels of HDL and apoA-I among ‘A’ allele carriers as compared to GG (patients). Our study, first of its kind from India, suggests that ‘A’ allele may contribute to severity of CAD and low levels of HDL & apoA-I. However, an in depth study with a larger set of sample is necessary.