G protein beta3 subunit variant and essential hypertension in Japanese

Enhanced G protein activation has been implicated to underlie the increased sodium-proton transport in blood cells, an impaired characteristic observed in 30% to 50% of patients with essential hypertension. Recently, significant association between a C825T polymorphism of the gene encoding the G protein beta3 subunit and hypertension was demonstrated in a white population, together with the finding that the T825 variant might be related to alternative splicing through unidentified mechanisms. We therefore investigated the disease relevance of this candidate gene by conducting an association study in a relatively large Japanese population. Participants comprised 718 hypertensive case subjects (without diabetes mellitus), 515 normotensive control subjects, and 191 hypertensive subjects with borderline or established diabetes mellitus; all individuals were recruited at a single institution. Genotype distribution of the C825T polymorphism was compared between hypertensive subjects, with or without diabetes, and the control group with chi2 statistics. No significant association was observed in the present study. Results were still not significant when the case group was subdivided according to more stringent classification criteria. Allele frequencies of T825 proved to be almost concordant among the 3 study groups and higher in Japanese (49.0% to 49.6%) compared with a reported prevalence of 25% to 31% in whites. Our data suggest that the T825 variant of the G protein beta3 subunit gene is unlikely to constitute major susceptibility for essential hypertension in the Japanese population studied. However, further investigation is required to answer the question of whether the lack of association reflects ethnic differences in the nature of genetic susceptibility loci.