Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.
Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci.
Cohen
J C
JC
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas 75235-9052.
Wang
Z
Z
Grundy
S M
SM
Stoesz
M R
MR
Guerra
R
R
D016632:Apolipoprotein A-I / Q000235:genetics; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D001483:Base Sequence; D015984:Causality; D008076:Cholesterol, HDL / Q000097:blood*; D014644:Genetic Variation; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009679:Nuclear Family; D013223:Statistics as Topic / Q000379:methods
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008076:Cholesterol, HDL; C022205:apolipoprotein A-IV; D008049:Lipase