Multiple Genetic Determinants of Variation of Plasma Lipoproteins in Alberta Hutterites

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Abstract
We hypothesized that variation of nine candidate genes in lipoprotein metabolism would be associated with variation in fasting plasma lipoprotein variables in 718 Alberta Hutterites, a genetic isolate. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apolipoprotein (apo) B ( APOB ), paraoxonase ( PON ), lipoprotein lipase ( LPL ), VLDL receptor ( VLDLR ), apo CIII ( APOC3 ), LDL receptor–related protein ( LRP ), hepatic lipase ( HL ), LDL receptor ( LDLR ), and apo E ( APOE ). Using a multivariate analysis, we found that (1) genotypes of APOB , PON , LPL , LDLR , and APOE were significantly associated with variation of plasma apo B–related traits; (2) genotypes of PON , LPL , and APOC3 were significantly associated with variation in plasma triglycerides; and (3) genotypes of VLDLR , APOC3 , LDLR , and APOE were significantly associated with variation in plasma apo AI and HDL cholesterol. Regression analysis showed that between 3.2% and 7.8% of the total variation in plasma lipoproteins was accounted for by variation in the candidate genes tested. The observations demonstrate a modest but significant genetic component of variation in plasma lipoprotein levels that is due to the candidate genes studied in this normolipemic human genetic isolate.