J. Lipid Res.
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A more recent version of this article appeared on May 1, 2005

Papers In Press, published online ahead of print February 16, 2005
J. Lipid Res., doi:10.1194/jlr.M400405-JLR200
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Submitted on October 13, 2004
Revised on January 28, 2005
Accepted on February 3, 2005

Alcohol intake modulates the genetic association between HDL cholesterol and the PPAR-gamma 2 Pro12Ala polymorphism

Stefan-Martin Brand-Herrmann, Tatiana Kuznetsova, Andreas Wiechert, Katarzyna Stolarz, Valerie Tikhonoff, Klaus Schmidt-Petersen, Ralph Telgmann, Edoardo Casiglia, Ji-Guang Wang, Lutgarde Thijs, Jan A. Staessen, and Eva Brand

Department of Molecular Genetics of Cardiovascular Disease, Institute for Arteriosclerosis Research, Muenster 48149

Corresponding Author: StefanMartin.BrandHerrmann{at}ukmuenster.de

The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor (PPAR)-gamma impacts on plasma lipids, but to what extent alcohol intake interferes with the genotype-phenotype relation remains unknown. In the framework of the European Project on Genes in Hypertension, we randomly recruited 251 nuclear families (433 parents and 493 offspring) in Cracow (Poland), Novosibirsk (Russia) and Mirano (Italy). Nine-hundred and twenty six participants in whom all serum lipid variables and information on alcohol consumption was available were genotyped for the PPAR-gamma 2 Pro12Ala polymorphism. 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) as well as QTDT (P=0.007), Italian offspring carrying the Ala12 allele had higher serum HDL cholesterol than non-carriers. With adjustment for appropriate confounders, HDL cholesterol levels were on average 0.086 mmol/L (P=0.001) higher in drinkers than in non-drinkers. In GEE, we observed a significant genotype-by-alcohol interaction. Compared to Pro12 homozygotes, Ala12 allele carriers had higher serum total and HDL cholesterol level if they regularly consumed alcohol, with the opposite trend occurring in non-drinkers. This genotype-by-alcohol interaction was due to alcohol intake per se and independent of the type of alcoholic beverage and more pronounced in moderate than 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 impact on cardiovascular prognosis.


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