G-protein beta 3 subunit gene (GNB3) variant in causation of essential hypertension

Essential hypertensives display enhanced signal transduction through pertus sis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta 3 subunit gene (GNB3) induces formation of a splice v ariant (G beta 3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients ( frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian whi te hypertensives. This involved an extensively examined cohort of 110 hyper tensives, each of whom were the offspring of 2 hypertensive parents, and 18 9 normotensives whose parents were both normotensive beyond age 50 years. G enotyping was performed by polymerase chain reaction and digestion with Bse DI, which either cut (C allele) or did not cut (T allele) the 268-bp polyme rase chain reaction product. T allele frequency in the hypertensive group w as 0.43 compared with 0.25 in the normotensive group (chi(2)=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretr eatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (me an+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA), Blood p ressures were higher in female hypertensives with a T allele (P=0.006 for s ystolic and 0.0003 for diastolic by ANOVA) than they were in male hypertens ives, In conclusion, the present study of a group with strong family histor y supports a role for a genetically determined, physiologically active spli ce variant of the G protein beta 3 subunit gene in the causation of essenti al hypertension.