Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease: Analysis of a large pedigree from the bogalusa heart study

I. M. Heiba, C. A. DeMeester, Y. R. Xia, A. Diep, Varghese George, C. I. Amos, S. R. Srinivasan, G. S. Berenson, R. C. Elston, A. J. Lusis

Research output: Contribution to journalArticle

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Abstract

A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL- C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL- C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume47
Issue number6
DOIs
StatePublished - Nov 9 1993

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Pedigree
Apolipoproteins B
HDL Cholesterol
Lipoproteins
Coronary Artery Disease
Cholesterol Ester Transfer Proteins
LDL Cholesterol
Lipoprotein Lipase
Apolipoprotein A-I
VLDL Cholesterol
Minisatellite Repeats
Haptoglobins
Lecithins
Transferases
Heart Diseases
Triglycerides
Alleles
Cholesterol
Genes

Keywords

  • association
  • candidate genes
  • cholesterol
  • sib-pair linkage
  • triglyceride

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease : Analysis of a large pedigree from the bogalusa heart study. / Heiba, I. M.; DeMeester, C. A.; Xia, Y. R.; Diep, A.; George, Varghese; Amos, C. I.; Srinivasan, S. R.; Berenson, G. S.; Elston, R. C.; Lusis, A. J.

In: American Journal of Medical Genetics, Vol. 47, No. 6, 09.11.1993, p. 875-883.

Research output: Contribution to journalArticle

Heiba, I. M. ; DeMeester, C. A. ; Xia, Y. R. ; Diep, A. ; George, Varghese ; Amos, C. I. ; Srinivasan, S. R. ; Berenson, G. S. ; Elston, R. C. ; Lusis, A. J. / Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease : Analysis of a large pedigree from the bogalusa heart study. In: American Journal of Medical Genetics. 1993 ; Vol. 47, No. 6. pp. 875-883.
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abstract = "A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5{\%} nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1{\%} nominal significance level, CETP [TaqI(B)] showed significant association with LDL- C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL- C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5{\%} nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease.",
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AU - George, Varghese

AU - Amos, C. I.

AU - Srinivasan, S. R.

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