G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women
G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women
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DOI：
10.1097/00004872-200411000-00014
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发表时间：
2004-11
影响因子：
4.9
通讯作者：
A. Matsuo;T. Katsuya;K. Ishikawa;K. Sugimoto;Y. Iwashima;Koichi Yamamoto;M. Ohishi;H. Rakugi;T. Ogihara
中科院分区：
文献类型：
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作者：
A. Matsuo;T. Katsuya;K. Ishikawa;K. Sugimoto;Y. Iwashima;Koichi Yamamoto;M. Ohishi;H. Rakugi;T. Ogihara
目的硫氮化物敏感的钠氯共转运体(TSC)位于远端肾小管。TSC基因的几个突变导致吉特尔曼综合征，这是一种常染色体隐性遗传病，特征是低血压和低钾血症。最近，瑞典报道了TSC基因(Arg904Gln，G2736A；Thr465Thr，C1420T；Gly264Ala，G816C)与原发性高血压的关联。我们研究了日本人原发性高血压与TSC基因的遗传关系。设计参与者来自大阪大学医院的门诊患者。我们调查了386名高血压患者和371名血压正常的受试者。方法采用TaqMan聚合酶链式反应方法检测TSC基因G2736A、C1420T、G816C等位基因，并用美国北卡罗来纳州卡里市SAS研究所的JMP 5.0.1J软件进行统计学分析。A2736和T1420的等位基因频率分别为6.0和3.0%，未检测到G816C多态。只有G2736A基因多态性与高血压患病率显著相关(P<；0.04)，在A2736等位基因携带者中估计的优势比为1.8(95%可信区间1.1-3.0)。在A2736携带者中，女性(n=413)患高血压的优势比增加到2.2(1.1~4.9)，在早发高血压的女性(⩽5 0岁)中进一步增加到3.3(1.4~8.0)。此外，在本研究(n=2)和瑞典研究(n=5)中，所有携带纯合子A2736等位基因的受试者均为高血压。结论TSC基因G2736A多态性是日本女性高血压的遗传易感因素。
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 (⩽ 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.