Population genetics of apolipoprotein A-4, E, and H polymorphisms in Yanomami Indians of northwestern Brazil: associations with lipids, lipoproteins, and carbohydrate metabolism.

Using isoelectric focusing and immunoblotting techniques, we screened 96 serum samples from Yanomami Indians of northwestern Brazil to determine structural variation at three apolipoprotein loci: A4, E, and H. The APO-H locus, which is commonly polymorphic in white and black samples, was found to be monomorphic. At the APO-E locus only two alleles, APOE3 and APOE4, rather than the three-allele polymorphism commonly seen in Caucasians, was observed. At the APO-A4 locus no example of the APOA42 allele, found in Caucasians, was detected. However, the frequency of the less common APOA44 allele was above what has been observed in any other population. We investigated the impact of genetic variation at both polymorphic loci on quantitative differences in lipids, apolipoproteins, serum glucose, glycated hemoglobin, and uric acid. Contrary to the cholesterol-elevating effect of APOE4 reported elsewhere, in both univariate analyses and after adjustments for age, sex, weight, and height, APOE4 was associated with about a 4% lower mean serum cholesterol. Only after adjustment was this association statistically significant. The APOE4 allele was significantly associated with unadjusted APO-A1 and APO-E levels but not with any other dependent variable; associations with adjusted APO-A1, APO-C2, and uric acid also approached standard levels of statistical significance (p < or = 0.05). In univariate analyses the APOA44 allele was significantly associated with APO-B, serum glucose, percent glycated hemoglobin, and uric acid, but no significant associations were observed after dependent variables were adjusted for age, sex, weight, and height. These results support the notion that apolipoprotein distributions and their associations with lipid and carbohydrate metabolism show ethnic variability.