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Published Online
on September 18, 2006

Hypertension. 2006
Published online before print September 18, 2006, doi: 10.1161/01.HYP.0000242485.23148.bb
A more recent version of this article appeared on November 1, 2006
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Submitted on June 16, 2006
Revised on July 18, 2006

Extensive Genetic Analysis of 10 Candidate Genes for Hypertension in Japanese

Naoharu Iwai*; Kazuaki Kajimoto; Yoshihiro Kokubo; and Hitonobu Tomoike

From the National Cardiovascular Center, Osaka, Japan.

* To whom correspondence should be addressed. E-mail: iwai{at}ri.ncvc.go.jp.

Abstract--The identification of genes that contribute to essential hypertension has been hampered because of a lack of statistical power and problems with multiple testing. In the present study, we performed association analyses between the 161 single nucleotide polymorphisms of 10 candidate genes and hypertension in a Japanese population recruited from the Suita Study (n=3654). We found that 5 polymorphisms in the 3 genes (SLC9A2, UMOD, and ELN) were associated with hypertension status, and 4 of these 5 polymorphisms were also associated with blood pressure values with a classical criterion of P<0.05. However, when a Bonferroni correction for multiple testing was applied, none of the polymorphisms were associated with blood pressure levels. We also performed association analyses between these 5 polymorphisms and intermediate phenotypes corresponding with the functions of candidate genes, including the renin/aldosterone profile, plasma uric acid levels, and pulse wave velocity. The ELN 3'-untranslated region (-/A) polymorphism was found to significantly affect pulse wave velocity, an indicator of arterial stiffness. Associations of the ELN 3'-untranslated region (-/A) polymorphism with hypertension and pulse wave velocity were reconfirmed in another set of the study population. Thus, ELN seems to contribute to blood pressure regulation by affecting arterial stiffness in Japanese.


Key words: hypertension • genetics • polymorphism • elastin




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