Published Online
on January 27, 2003

A more recent version of this article appeared on February 1, 2003

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Submitted on September 9, 2002
Revised on October 8, 2002

Peroxisome Proliferator-Activated Receptor- Coactivator-1 Gene Locus. Associations with Hypertension in Middle-Aged Men

Hannes Oberkofler; Bertram Hölzl; Harald Esterbauer; Mingqiang Xie; Bernhard Iglseder; Franz Krempler; Bernhard Paulweber; and Wolfgang Patsch^*

From the Department of Laboratory Medicine (H.O., H.E., M.X., W.P.), the First Department of Internal Medicine (B.H., B.P.), and the Department of Neurology (B.I.), Landeskliniken, Salzburg; and the Department of Internal Medicine, Krankenhaus Hallein (F.K.), Austria.

^* To whom correspondence should be addressed. E-mail: w.patsch{at}lks.at.

Abstract--Peroxisome proliferator-activated receptor- coactivator-1 (PPARGC1/PGC-1) is a transcriptional coactivator of nuclear hormone receptors implicated in blood pressure regulation. We therefore ascertained whether the PPARGC1 gene locus is associated with hypertension. We studied associations of 3 polymorphisms in PPARGC1 transcripts with hypertension in 683 middle-aged men and 530 middle-aged women of a cross-sectional Austrian population. Hypertension was defined by average values of systolic or diastolic ambulatory blood pressure readings (taken between 7 AM and 10 PM) above 140 and/or 90 and/or use of antihypertensive medication. Among the 3 polymorphic sites, genotype distributions associated with Gly482Ser differed by hypertension status in men (P=0.0038), but not in women. The less common Ser482 allele was associated with a modest, but significant, reduction in the prevalence of hypertension in men. The distribution of 3 loci haplotypes also differed in men with and without hypertension (P=0.015). Despite its moderate effect, but because of its high frequency (64%), the more common risk allele contributed to hypertension in 35% (95% CI 16% to 54%) of our male population. These results suggest, but do not prove, that PPARGC1 participates in blood pressure control, and sequence substitutions at its gene locus confer an increased risk of hypertension to a substantial proportion of men.

Key words: genetics • genes • gender • haplotypes • polymorphism

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