A gene-gender interaction affecting plasma lipoproteins in a genetic isolate

The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation in their apolipoprotein (apo) E and lipoprotein lipase (LPL) genes would be associated with variation in fasting plasma lipoproteins. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apoE and LPL in 803 Hutterites. We observed that apoE and LPL genotypes were significantly associated with variations in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and apoB. When the data were subdivided by sex, apoE genotype was associated with plasma apoB-related traits in men, but LPL genotype was not. In contrast, LPL genotype was associated with plasma apoB-related traits in women, including triglycerides and LDL cholesterol. After accounting for age, body mass index, and colony of origin, the variation in these variables was much more significantly associated with LDL genotype than with apoE genotype in women but not in men. The association of LPL variation with plasma lipoproteins in women suggests that the functional effects of important structural elements within, flanking, or proximal to the LPL gene on chromosome 8p22 may be sex related.