C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic.
The T allele of the C825T polymorphism of the gene encoding the beta(3)-subunit of G proteins has been associated with increased sodium-hydrogen exchange and low renin in patients with essential hypertension. To assess its association with blood pressure response to diuretic therapy, we measured the C825T polymorphism in 197 blacks (134 men, 63 women) and 190 non-Hispanic whites (76 men, 114 women) with essential hypertension (mean+/-SD age 48+/-7 years), who underwent monotherapy with hydrochlorothiazide for 4 weeks. Mean declines in systolic and diastolic blood pressures were 6+/-2 (P:<0.001) and 5+/-1 (P:<0.001) mm Hg greater, respectively, in TT than in CC homozygotes. Responses in heterozygotes were intermediate between the homozygous groups. Other univariate predictors of greater blood pressure responses included black race, female gender, higher pretreatment blood pressure, older age, lower waist-to-hip ratio, and measures of lower renin-angiotensin-aldosterone system activity. After the effects of the other predictors were considered, the TT genotype remained a significant predictor of greater declines in systolic and diastolic blood pressures. Thus, the C825T polymorphism of the G protein beta(3)-subunit may help identify patients with essential hypertension who are more responsive to diuretic therapy.
Division of Hypertension, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA. turner.stephen@mayo.edu
S T
ST
Turner
G L
GL
Schwartz
A B
AB
Chapman
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E
Boerwinkle
D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000097:blood; D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D044469:Racial Groups; D012083:Renin / Q000097:blood; D012737:Sex Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D000450:Aldosterone; D012083:Renin; D020962:Heterotrimeric GTP-Binding Proteins