Polymorphisms in the peroxisome proliferator activated receptor alpha gene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians

Abstract

Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARalpha gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians.

Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p<0.05) in a subset of 435 individuals from the total study population (n=944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r(2)=0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2% vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p<0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction=0.0056) and apoCIII (p for interaction=0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V.

Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels.

Figure 1. Plasma apo-CIII and TG levels in Caucasians and African-Americans according to the PPARα L162V SNP

Means ± S.E. Means were adjusted for age, sex, BMI, waist, current smoking, alcohol consumption, exercise levels, estrogen use and presence of hypertension and type 2 diabetes mellitus