Variations in the promoter region of the apolipoprotein A-1 gene influence plasma lipoprotein(a) levels in Asian Indian neonates from Singapore

Abstract

We studied the influence of two DNA polymorphisms (-75 bp G/A and +83 bp C/T) in the promoter region of the apolipoprotein A-1 (apoA1) gene on cord plasma level of lipoprotein(a) [Lp(a)] in 1076 newborns of both genders from the three major ethnic groups in Singapore-Chinese, Malays, and Asian Indians. The frequency of the A: allele at -75 bp in the Indians was significantly lower than the Chinese and Malays. There was no linkage disequilibrium between the two sites studied. Both polymorphic sites were not significantly associated with any lipid factors except for Lp(a) levels in the Asian Indians. The AA and CC homozygotes were significantly associated with lower Lp(a) levels. These associations were specific only to the male Indian neonates. The genetic variations at the -75 and +83 bp explained 6.9% and 7.2%, respectively, of the total variability of plasma Lp(a) levels at birth in the Asian Indians. The Lp(a) levels were also significantly different between composite genotypes in the order GG/TT > GA/CT > GG/CT > GA/CC > GG/CC > AA/CC. The effects of the two polymorphisms seem to be additive as the composite genotypes were able to explain 14% of the Lp(a) variance, equivalent to the sum of the two constituent sites. Our results showed that there is significant ethnic- and gender-specific influence of the apoA1 gene on plasma Lp(a) levels at birth that is inherent and independent of known gene-environment interactions.