ETHNIC VARIATION AND IN-VIVO EFFECTS OF THE -93T-]G PROMOTER VARIANT IN THE LIPOPROTEIN-LIPASE GENE

Recently, a (t-->g) transition at nucleotide -93 in the lipoprotein li pase (LPL) gene promoter has been observed in Caucasians. Here, we hav e compared the frequency of the -93g carriers in three distinct popula tions (Caucasians, South African Blacks, and Chinese). The carrier fre quency in the Caucasian population was 1.7% (4/232), which was in cont rast to the South African Black population, which had a frequency for this allele of 76.4% (123/161) of the individuals tested. This transit ion was not observed in the Chinese population under study. Near compl ete linkage disequilibrium between the -93g and the previously describ ed D9N mutation was observed in the Caucasian population but not in So uth African Blacks. To further assess the ancestral origins of these D NA changes, DNA haplotyping using a CA repeal 5' to these substitution s was performed. The -93t allele was associated with only a few specif ic dinucleotide repeat sizes. In contrast, the -93g allele occurred on chromosomes with many different repeat lengths. The broad distributio n of repeats on -93g carrying chromosomes, their high frequency in the South African Black population, and the conservation of the -93g alle le among different species may suggest that the -93g allele is the anc estral allele on which a transition to t and the D9N mutations arose. The very high frequency of the -93g allele distinct from the N9 allele in a cohort of Black South Africans allowed us to specifically assess the phenotypic effects of the -93g allele on lipids. Individuals homo zygous for the g allele at -93 showed mildly decreased triglycerides c ompared with individuals homozygous for the t allele (1.14+/-0.66 mmol /L versus 0.82+/-0.3; P=.04). Thus, the -93g allele in this cohort is associated with low plasma triglyceride levels.