Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Quebec Family Study

The associations between the S447X, BamHI, HindIII and PvuII DNA variants o f the lipoprotein lipase (LPL) gene and indicators of body fat, fat distrib ution and plasma lipids and insulin were studied in the Quebec Family Study cohort. Strong linkage disequilibrium among all the markers was observed. For the S447X polymorphism, plasma very low density lipoprotein (VLDL)-chol esterol (chol) (P < 0.001), total triglyceride (TG) (P = 0.033) and VLDL-TG (P < 0.001) levels were lower and high density lipoprotein (HDL)-chol leve l higher (P < 0.001) in the subjects homozygous or heterozygous for X447 (X 447 +, n = 160) compared to the homozygotes for the S447 allele (X447 -, n = 576). The BamHI, PvuII and HindIII polymorphisms were not associated with the plasma lipid values when all X447 allele carriers were removed. In add ition, the HindIII polymorphism as well as the HindIII and S447X markers co mbination influenced the insulin area under the curve during an oral glucos e tolerance test. We conclude that DNA sequence variation in the LPL gene c ontributes significantly to the variability in the levels of VLDL-chol, tot al- and VLDL-TG as well as HDL-chol. The effects of the other polymorphisms considered here are most likely mediated by their linkage disequilibrium w ith the S447X mutation. In addition, genetic variation at the LPL locus may , by an unknown mechanism, influence insulin metabolism but not body fat va riability. (C) 2001 Elsevier Science Ltd. All rights reserved.