Extensive genetic analysis of 10 candidate genes for hypertension in Japanese.

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.