Alcohol intake modulates the genetic association between HDL cholesterol and the PPARγ2 Pro12Ala polymorphism

被引:22
作者
Brand-Herrmann, SM [1 ]
Kuznetsova, T
Wiechert, A
Stolarz, K
Tikhonoff, V
Schmidt-Petersen, K
Telgmann, R
Casiglia, E
Wang, JG
Thijs, L
Staessen, JA
Brand, E
机构
[1] Univ Munster, Leibniz Inst Arteriosclerosis Res, D-4400 Munster, Germany
[2] Univ Munster, Dept Mol Genet Cardiovasc Dis, D-4400 Munster, Germany
[3] Univ Louvain, Dept Mol & Cardiovasc Res, Hypertens & Cardiovasc Rehabil Unit, Louvain, Belgium
[4] Inst Internal Med, Novosibirsk, Russia
[5] Univ Med Berlin, Charite, Dept Internal Med, Div Endocrinol & Nephrol, Berlin, Germany
[6] Jagiellonian Univ, Cardiac Dept 1, Krakow, Poland
[7] Univ Padua, Dept Clin & Expt Med, Padua, Italy
[8] Univ Clin Muenster, Dept Internal Med D, Munster, Germany
关键词
peroxisome proliferator-activated receptor gamma 2; high density lipoprotein cholesterol; genotype-alcohol interaction;
D O I
10.1194/jlr.M400405-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The peroxisome proliferator-activated receptor gamma (PPAR gamma) Pro12Ala polymorphism affects plasma lipids, but to what extent alcohol intake interferes with this association remains unknown. We randomly recruited 251 nuclear families ( 433 parents and 493 offspring) in the framework of the European Project on Genes in Hypertension study and genotyped 926 participants in whom all serum lipid variables and information on alcohol consumption were available for PPAR gamma 2 Pro12Ala. Genotype- phenotype relations were assessed using generalized estimating equations ( GEE) and a quantitative transmission disequilibrium test (QTDT). The Ala12 allele was more frequent in Novosibirsk (0.17) than in Cracow (0.12) and Mirano (0.11) ( P < 0.01). Using GEE ( P = 0.03) or QTDT ( P = 0.007), Italian offspring carrying the Ala12 allele had higher serum HDL cholesterol than noncarriers. HDL cholesterol levels were on average 0.086 mmol/ l ( P = 0.001) higher in drinkers than in nondrinkers. Compared with Pro12 homozygotes, Ala12 allele carriers consuming alcohol had higher serum total and HDL cholesterol, with the opposite trend occurring in nondrinkers. This genotype-alcohol interaction was independent of the type of alcoholic beverage and more pronounced in moderate than in heavy drinkers. We conclude that alcohol intake modulates the relation between the PPAR gamma 2 Pro12Ala and HDL cholesterol level and that, therefore, the Pro12Ala polymorphism, pending confirmation of our findings, might affect cardiovascular prognosis.
引用
收藏
页码:913 / 919
页数:7
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