APOLIPOPROTEIN-B GENE POLYMORPHISMS ARE ASSOCIATED WITH LIPID-LEVELS IN MEN OF SOUTH ASIAN DESCENT

Three polymorphic sites of the apolipoprotein B gene - the insertion/deletion signal peptide, XbaI and EcoRI sites - were examined in a sample of 107 healthy men and in 46 men with evidence of coronary heart disease selected from a large population survey of South Asians aged 40-69 in London, U.K. There were no significant differences in allele frequencies between cases and controls. Frequencies of the ins (insertion) and X- (absence of XbaI cutting site) alleles were higher in South Asians than in Europeans studied previously (South Asians versus Europeans ins: 0.80 vs. 0.68, P < 0.025; X- : 0.71 vs. 0.47-0.56, P < 0.001). The del allele was associated with higher levels of total cholesterol (P < 0.05) and the X + allele with lower levels of HDL cholesterol (P < 0.05), and thus both polymorphisms were associated with differences in the ratio of HDL cholesterol to total cholesterol (ins/del, P < 0.01; XbaI, P < 0.001). Mean waist-hip girth ratio was lower in the 10 men homozygous for the X+ allele than in the 42 men with X -/X + and 55 men with X-/X - genotypes; the means (+/- SEM) were 0.92 +/- 0.02, 0.97 +/- 0.01 and 0.96 +/- 0.01 respectively (P = 0.03). These data suggest that genetic variation in linkage disequilibrium with the XbaI and ins/del polymorphisms of the apo B gene contributes to the determination of total cholesterol and HDL cholesterol levels and possibly to obesity in South Asians.