A high prevalence of Gitelman's syndrome mutations in Japanese
A high prevalence of Gitelman's syndrome mutations in Japanese
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DOI：
10.1291/hypres.27.327
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发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Iwai, N
中科院分区：
文献类型：
--
作者：
Tago, N;Kokubo, Y;Iwai, N
虽然Gitelman综合征（GS）被认为是一种罕见的疾病，但它是一种常染色体隐性表型，杂合子受试者的频率可能高于怀疑。本研究的目的是评估GS在日本的患病率和杂合子GS突变对血压水平的影响。我们使用TaqMan系统检测9个日本人已报道的SLC 12 A3 Gitelman综合征突变。然后，我们在Suita研究中招募的1，852名受试者中进行了这些突变与血压之间的关联研究，这些受试者代表了日本的一般人群。在这1,852名受试者中，我们分别在56名、14名、1名、1名和47名受试者中检测到T180 K、A569 V、L 623 P、R642 C和L 849 H杂合子基因型。GS突变的总频率为（56+14+1+ 1+47）/（1，852 × 2）=0.0321，远高于推测值。这意味着我们应该期望在15.6名日本人中找到1名具有杂合GS突变的受试者，或者我们应该在10，000名日本人中找到10.3名GS受试者。尽管T180 K、A569 V或L 849 H基因型杂合子受试者的血压水平与野生型受试者无显著差异，但GS突变受试者的尿液pH值显著高于无突变受试者。总之，GS可能是日本人低血压的主要原因之一。
Although Gitelman's syndrome (GS) is considered a rare disorder, it is an autosomal recessive phenotype and the frequency of heterozygote subjects might be higher than suspected. The purpose of this study was to assess the prevalence of GS in Japanese and the effects of heterozygous GS mutations on blood pressure levels. We used the TaqMan system to detect 9 Gitelman's syndrome mutations in SLC12A3 that have been reported in Japanese. We then conducted association studies between these mutations and blood pressure in 1,852 subjects recruited from the Suita study, representing the general population in Japan. Among these 1,852 subjects, we detected the T180K, A569V, L623P, R642C, and L849H heterozygote genotypes in 56, 14, 1, 1, and 47 subjects, respectively. The overall frequency of GS mutations was (56+14+1+ 1+47) / (1,852x2)=0.0321, which was much higher than suspected. This means we should expect to find one subject with a heterozygous GS mutation among 15.6 Japanese or that we should find 10.3 GS subjects among 10,000 Japanese. Although the blood pressure levels of subjects heterozygous for the T180K, A569V, or L849H genotype were not significantly different from those of wild-type subjects, urine pH in subjects with GS mutations was significantly higher than that in subjects without mutations. In conclusion, GS could be one of the major causes of low blood pressure in Japanese.