HAPLOTYPES OF ALDOSTERONE SYNTHASE (CYP11B2) GENE IN THE GENERAL POPULATION OF JAPAN: THE OHASAMA STUDY
HAPLOTYPES OF ALDOSTERONE SYNTHASE (CYP11B2) GENE IN THE GENERAL POPULATION OF JAPAN: THE OHASAMA STUDY
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日本普通人群中醛固酮合酶 (CYP11B2) 基因的单倍型：OHASAMA 研究
DOI：
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发表时间：
2001
影响因子：
12.3
通讯作者：
Y. Imai
中科院分区：
文献类型：
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作者：
M. Matsubara;Fumiko Omori;S. Fujita;H. Metoki;M. Kikuya;Tohru Fujiwara;T. Araki;Y. Imai
自从发现了一种可诱导孟德尔式高血压的嵌合型醛固酮合酶以来，醛固酮合酶（CYP11B2）的多态性已成为高血压相关分子研究的主要靶点之一。迄今为止，已在高加索人群中鉴定出CYP11 B2的四种多态性变体，启动子区的− 344 T/C，内含子2的基因转换，2713 A/G（外显子3），其在密码子173处从Lys转换为Arg（K173 R），以及4986 T/C（外显子7），其在密码子386处从瓦尔转换为Ala（V386 A）。然后，− 344 T/C多态性与内含子2或K173 R突变的基因转换之间的连锁不平衡已经被描述，表明高加索人存在遗传单倍型。由于内含子2或V386 A突变的基因转换在日本人群中的存在仍然是未知的，所有这些多态性进行了检查，以确定CYP11 B2单倍型的日本人，使用的DNA样本1290名参与者的Ohasama研究，谁代表了一般人口的北方日本的农村社区。分子生物学分析表明，在日本人群中存在内含子2的基因转换，但没有V386A突变。− 344 T/C多态性与K173 R突变之间存在完全连锁不平衡。虽然− 344 T等位基因与内含子2的基因转换或与正常内含子2连锁，但− 344 C等位基因与正常内含子2完全连锁。这些结果表明，在一般日本人群中，CYP11 B2存在3种等位基因单倍型：− 344 C（内含子2和173 R正常）、− 344 T（内含子2和173 K正常）和− 344 T（内含子2和173 K转换）。频率（总计1.0）分别为0.35、0.53和0.12。等位基因单倍型的存在被认为是对CYP11B2个体多态性的补充遗传信息，以确定CYP11B2多态性与高血压之间的联系。
Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypertension. To date, four polymorphic variants of CYP11B2, −344T/C at promoter region, a gene conversion in intron 2, 2713A/G (in exon 3) which converts from Lys to Arg at codon 173 (K173R), and 4986T/C (in exon7) which converts from Val to Ala at codon 386 (V386A), have been identified in Caucasian population. Then, linkage disequilibrium between −344T/C polymorphism and a gene conversion in intron 2 or K173R mutation has been described, suggesting the presence of genetic haplotypes in Caucasians. Since the presence of a gene conversion in intron 2 or V386A mutation was still unknown in the Japanese population, all these polymorphisms were examined together to determine the CYP11B2 haplotypes of Japanese, using DNA samples from 1290 participants of the Ohasama study, who represent the general population of a rural community of northern Japan. Molecular analyses demonstrated the presence of a gene conversion of intron 2, but the absence of V386A mutation in Japanese population. The complete linkage disequilibrium between −344T/C polymorphism and K173R mutation was noted. Although −344T allele was linked either with a gene conversion in intron 2 or with normal intron 2, −344C allele was completely linked with normal intron 2. These results indicate the presence of 3 allelic haplotypes of CYP11B2, −344C with normal intron 2 and 173R, −344T with normal intron 2 and 173K, and −344T with converted intron 2 and 173K, in the general Japanese population. The frequency (total 1.0) was 0.35, 0.53, and 0.12, respectively. The presence of allelic haplotypes is considered to be an additional genetic information to individual polymorphism of CYP11B2 to determine the linkage between CYP11B2 polymorphisms and hypertension.
影响因子：
2.1
作者：
WHITE, PC;SLUTSKER, L
通讯作者：
SLUTSKER, L
影响因子：
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作者：
CURNOW, KM;TUSIELUNA, MT;WHITE, PC
通讯作者：
WHITE, PC