Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels

Len A. Pennacchio, Michael Olivier, Jaroslav A. Hubacek, Ronald M. Krauss, Edward M. Rubin, Jonathan C. Cohen

Research output: Contribution to journalArticle

337 Citations (Scopus)

Abstract

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in ∼16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n = 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

Original languageEnglish (US)
Pages (from-to)3031-3038
Number of pages8
JournalHuman Molecular Genetics
Volume11
Issue number24
StatePublished - Nov 15 2002

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Haplotypes
Triglycerides
Genes
Hispanic Americans
African Americans
Apolipoprotein A-V
Population
Diet
High Fat Diet
Ethnic Groups
Codon
Tryptophan
Serine
Single Nucleotide Polymorphism
Alleles
Carbohydrates
Phenotype

ASJC Scopus subject areas

  • Genetics

Cite this

Pennacchio, L. A., Olivier, M., Hubacek, J. A., Krauss, R. M., Rubin, E. M., & Cohen, J. C. (2002). Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels. Human Molecular Genetics, 11(24), 3031-3038.

Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels. / Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

In: Human Molecular Genetics, Vol. 11, No. 24, 15.11.2002, p. 3031-3038.

Research output: Contribution to journalArticle

Pennacchio, LA, Olivier, M, Hubacek, JA, Krauss, RM, Rubin, EM & Cohen, JC 2002, 'Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels', Human Molecular Genetics, vol. 11, no. 24, pp. 3031-3038.
Pennacchio LA, Olivier M, Hubacek JA, Krauss RM, Rubin EM, Cohen JC. Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels. Human Molecular Genetics. 2002 Nov 15;11(24):3031-3038.
Pennacchio, Len A. ; Olivier, Michael ; Hubacek, Jaroslav A. ; Krauss, Ronald M. ; Rubin, Edward M. ; Cohen, Jonathan C. / Two independent apolipoprotien A5 haplotypes influence human plasma triglyceride levels. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 24. pp. 3031-3038.
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