Polymorphisms in the peroxisome proliferator activated receptor α gene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians

Min-Jeong Shin, Alka M. Kanaya, Ronald M. Krauss

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARα gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians. Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p < 0.05) in a subset of 435 individuals from the total study population (n = 944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r 2 = 0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2% vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p < 0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction = 0.0056) and apoCIII (p for interaction = 0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V. Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalAtherosclerosis
Volume198
Issue number2
DOIs
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Fingerprint

Apolipoprotein C-III
Peroxisome Proliferator-Activated Receptors
African Americans
Single Nucleotide Polymorphism
Triglycerides
Genes
Alleles
Linkage Disequilibrium
Homozygote
Waist Circumference
Gene Frequency
Population
Lipoproteins
Body Mass Index
Lipids

Keywords

  • Apolipoprotein CIII
  • Gene polymorphism
  • PPARα
  • Race
  • Triglyceride

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{aea2a26f14a1437081ce48ad7b0aba28,
title = "Polymorphisms in the peroxisome proliferator activated receptor α gene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians",
abstract = "Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARα gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians. Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p < 0.05) in a subset of 435 individuals from the total study population (n = 944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r 2 = 0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2{\%} vs. 27.3{\%} for rs4253728, 1.5{\%} vs. 6.1{\%} for L162V, both p < 0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction = 0.0056) and apoCIII (p for interaction = 0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V. Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels.",
keywords = "Apolipoprotein CIII, Gene polymorphism, PPARα, Race, Triglyceride",
author = "Min-Jeong Shin and Kanaya, {Alka M.} and Krauss, {Ronald M.}",
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T1 - Polymorphisms in the peroxisome proliferator activated receptor α gene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians

AU - Shin, Min-Jeong

AU - Kanaya, Alka M.

AU - Krauss, Ronald M.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARα gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians. Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p < 0.05) in a subset of 435 individuals from the total study population (n = 944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r 2 = 0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2% vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p < 0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction = 0.0056) and apoCIII (p for interaction = 0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V. Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels.

AB - Background: We tested whether single nucleotide polymorphisms (SNPs) in the PPARα gene (PPARA) are associated with variations in levels of plasma apolipoprotein CIII (apoCIII) levels, as well as other lipids and lipoproteins, in African-Americans and Caucasians. Methods and results: We initially identified an intronic SNP (rs4253728) in PPARA that was associated with plasma apoCIII level (p < 0.05) in a subset of 435 individuals from the total study population (n = 944; 335 African-Americans and 609 Caucasians). This SNP was then genotyped in a second subset of 476 individuals (total 911 subjects with available data), and a previously described PPARA coding SNP (L162V) which was shown to be in moderate linkage disequilibrium with the intronic SNP (r 2 = 0.18) was genotyped in 928 subjects from the same study population. The minor allele frequencies for both SNPs were significantly lower in African-Americans compared with Caucasians (7.2% vs. 27.3% for rs4253728, 1.5% vs. 6.1% for L162V, both p < 0.0001). African-Americans had significantly lower levels of TG and apoCIII compared with Caucasians after adjusting for age, sex, body mass index (BMI), waist circumference and other baseline characteristics. However, racial differences in TG levels were attenuated after adjusting for apoCIII levels. The minor alleles for both PPARA SNPs were associated with higher TG and apoCIII levels. Race modified the associations of L162V with TG (p for interaction = 0.0056) and apoCIII (p for interaction = 0.0011). Levels of both TG and apoCIII were lower in African-American but not Caucasian homozygotes for the major allele compared with carriers of the minor allele. Similar results were obtained for the intronic SNP, but the findings were no longer significant in a model that also contained L162V. Conclusions: Two PPARA SNPs, L162V and rs4253728 (intronic), are less prevalent in African-Americans than in Caucasians and in African-Americans only are associated with higher apoCIII and TG levels.

KW - Apolipoprotein CIII

KW - Gene polymorphism

KW - PPARα

KW - Race

KW - Triglyceride

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U2 - 10.1016/j.atherosclerosis.2007.10.004

DO - 10.1016/j.atherosclerosis.2007.10.004

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