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Clinical Significance of Sodium Metabolism-related Gene Polymorphisms in Salt-Sensitive Hypertension

钠代谢相关基因多态性在盐敏感性高血压中的临床意义

基本信息

批准号：
15590477
负责人：
YASUJIMA Minoru
金额：
$ 2.18万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

Thiazide-sensitive Na-Cl cotransporter (TSC) is the major NaCl transport pathway in the apical membrane of the renal distal convoluted tubule, which could be involved in the pathogenesis of salt-sensitive hypertension. Mutation of TSC is known to be responsible for Gitelman's syndrome, an autosomal recessive renal tubular disorder characterized by low blood pressure due to renal sodium wasting, hypokalemia, metabolic alkalosis, hypomagnesemia and normocalcemic hypocalciuria. Gitelman's syndrome is thought as a mirror image of salt-sensitive hypertension. We assessed mutational analysis of TSC gene in 36 patients with Gitelman' s syndrome, and this study revealed genetic backgrounds of salt-sensitive hypertension. We found 19 mutations include 8 novel mutations that were R261C, N406H, A523T, M672I, R1009Q, N1014K, deletion of C in the 9th exon and deletion of C in the 16th exon. Only 5 patients in northern area of Tohoku had deletion of C in the 16th exon suggesting that the specific mutation might be an area-dependent accumulation. We also investigated the association of those TSC mutations and 2711G/A (R904Q) polymorphism with hypertension. The case-control study consisted of 32 young hypertensive patients and 20 aged normotensive control subjects. We found no TSC mutations, and 2711G/A polymorphism was no differences in the genotype frequencies and the allele frequencies between hypertensives and normotensives. In addition, we assessed mutational analysis of TSC gene in 26 patients with hypokalemia (serum K concentration was under 3.5 mmol/l). As a result, we found 3 mutations, T180K, L849H and R919C. Five patients had heterozygous mutations and a patient had compound heterozygous mutations. The mutants frequency was 23%, and allele frequency was 13.5%. Further studies are needed to clarify clinical significance of NaCl reabsorption mechanisms including TSC in salt-sensitive hypertension.

噻嗪敏感Na-Cl共转运体（TSC）是肾远曲小管顶膜中主要的NaCl转运途径，可能参与盐敏感性高血压的发病机制。已知TSC突变可导致Gitelman综合征，这是一种常染色体隐性肾小管疾病，其特征是由于肾脏钠消耗、低钾血症、代谢性碱中毒、低镁血症和等钙血症低钙尿引起的低血压。吉特尔曼综合征被认为是盐敏感性高血压的镜像。我们评估了36例Gitelman综合征患者的TSC基因突变分析，该研究揭示了盐敏感性高血压的遗传背景。我们发现19个突变包括8个新突变，分别是R261C、N406H、A523T、M672I、R1009Q、N1014K，第9外显子C缺失和第16外显子C缺失。东北北部地区仅有5例患者在第16外显子缺失C，提示该特异性突变可能是一种区域依赖性积累。我们还研究了这些TSC突变和2711G/A （R904Q）多态性与高血压的关系。病例-对照研究包括32例青年高血压患者和20例老年正常血压对照组。我们没有发现TSC突变，2711G/A多态性在高血压患者和正常血压患者的基因型频率和等位基因频率上没有差异。此外，我们对26例低钾血症（血钾浓度低于3.5 mmol/l）患者的TSC基因进行了突变分析。结果，我们发现3个突变，T180K， L849H和R919C。杂合突变5例，复合杂合突变1例。突变体频率为23%，等位基因频率为13.5%。盐敏感性高血压患者包括TSC在内的盐重吸收机制的临床意义有待进一步研究。

项目成果

期刊论文数量（65）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Kotani N, et al.: "Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia"Am J Med. 116. 318-324 (2004)

Kotani N 等人：“脑脊液白细胞介素 8 浓度和带状疱疹后神经痛的后续发展”Am J Med。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis

钙通道1亚基基因分析及两例低钾性周期性麻痹患者临床研究

DOI：
发表时间：
2006
期刊：
J Endocrinol Invest 29-10
影响因子：
0
作者：
Sugie;M.;Asakura;E.;Zhao;Y.L.;Torita;S.;Nadai;M.;Baba;K.;Kitaichi;K.;Takagi;K.;Takagi;K.;Hasegawa;T.;Kageyama K
通讯作者：
Kageyama K

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