Objective: The thiazide-sensitive Na-Cl cotransporter (TSC) is located in the distal renal tubules. Several mutations of the TSC gene cause Gitelman's syndrome, which is an autosomal recessive disease characterized by low blood pressure and hypokalemia. Recently, an association between TSC gene polymorphisms (Arg904Gln, G2736A; Thr465Thr, C1420T; Gly264Ala, G816C) and essential hypertension has been reported in Sweden. We examined the genetic involvement of the TSC gene in essential hypertension in Japanese.
Design: Participants were recruited from outpatients of Osaka University Hospital. We investigated 386 hypertensive and 371 normotensive subjects.
Methods: Genotypes of TSC polymorphisms (G2736A, C1420T, G816C) were determined by the TaqMan polymerase chain reaction (PCR) method, and statistical significance was examined using JMP 5.0.1J (SAS Institute Inc., Cary, North Carolina, USA). The allele frequency of A2736 and T1420 was 6.0 and 3.0%, respectively, whereas we could not detect the G816C polymorphism in this study. Only the G2736A polymorphism was significantly associated with the prevalence of hypertension (P <0.04), and the estimated odds ratio was 1.8 (95% confidence interval, 1.1-3.0) in A2736 allele carriers. The odds ratio for hypertension in A2736 carriers was increased to 2.2 (1.1-4.9) in women (n=413), and further to 3.3 (1.4-8.0) in women with early onset of hypertension (< or = 50 years old). In addition, all subjects with the homozygous A2736 allele in this study (n=2) and the Swedish study (n=5) were hypertensive.
Conclusion: G2736A polymorphism of the TSC gene is a genetic predisposing factor for essential hypertension in Japanese women.