Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels

Jonathan C. Cohen, Zifen Wang, Scott M. Grundy, Marcia Regier Stoesz, Rudy Guerra

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2377-2384
Number of pages8
JournalJournal of Clinical Investigation
Volume94
Issue number6
StatePublished - Dec 1994

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Apolipoprotein C-III
Apolipoprotein A-I
Lipase
HDL Cholesterol
Liver
Cholesterol Ester Transfer Proteins
Siblings
Genes
Nuclear Family
Alleles

Keywords

  • apolipoprotein AI
  • cholesteryl ester transfer protein
  • hepatic lipase
  • lipoproteins HDL
  • lipoproteins HDL cholesterol

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels. / Cohen, Jonathan C.; Wang, Zifen; Grundy, Scott M.; Stoesz, Marcia Regier; Guerra, Rudy.

In: Journal of Clinical Investigation, Vol. 94, No. 6, 12.1994, p. 2377-2384.

Research output: Contribution to journalArticle

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abstract = "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.",
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