Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition

evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci

Xiangdong Bu, Craig H Warden, Yu Rong Xia, Cynthia De Meester, Donald L. Puppione, Scott Teruya, Beth Lokensgard, Siamac Daneshmand, Jane Brown, Richard J. Gray, Jerome I. Rotter, Aldons J. Lusis

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins.

Original languageEnglish (US)
Pages (from-to)639-648
Number of pages10
JournalHuman Genetics
Volume93
Issue number6
DOIs
StatePublished - Jun 1994

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Apolipoprotein A-II
Cholesterol Ester Transfer Proteins
Genetic Linkage
HDL Lipoproteins
Genetic Loci
Apolipoproteins
Apolipoproteins C
Apoprotein(a)
Apolipoprotein A-I
Lipoproteins
Apolipoprotein C-III
Apolipoproteins A
Genes
Chromosomes, Human, Pair 6
Lipoprotein Lipase
LDL Receptors
Apolipoproteins B
Apolipoproteins E
Microsatellite Repeats
HDL Cholesterol

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition : evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci. / Bu, Xiangdong; Warden, Craig H; Xia, Yu Rong; De Meester, Cynthia; Puppione, Donald L.; Teruya, Scott; Lokensgard, Beth; Daneshmand, Siamac; Brown, Jane; Gray, Richard J.; Rotter, Jerome I.; Lusis, Aldons J.

In: Human Genetics, Vol. 93, No. 6, 06.1994, p. 639-648.

Research output: Contribution to journalArticle

Bu, Xiangdong ; Warden, Craig H ; Xia, Yu Rong ; De Meester, Cynthia ; Puppione, Donald L. ; Teruya, Scott ; Lokensgard, Beth ; Daneshmand, Siamac ; Brown, Jane ; Gray, Richard J. ; Rotter, Jerome I. ; Lusis, Aldons J. / Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition : evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci. In: Human Genetics. 1994 ; Vol. 93, No. 6. pp. 639-648.
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abstract = "We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins.",
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AU - Warden, Craig H

AU - Xia, Yu Rong

AU - De Meester, Cynthia

AU - Puppione, Donald L.

AU - Teruya, Scott

AU - Lokensgard, Beth

AU - Daneshmand, Siamac

AU - Brown, Jane

AU - Gray, Richard J.

AU - Rotter, Jerome I.

AU - Lusis, Aldons J.

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