Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension
Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension
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DOI：
10.1002/humu.10047
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发表时间：
2002-01-01
期刊：
影响因子：
3.9
通讯作者：
Arinami, T
中科院分区：
文献类型：
--
作者：
Yamamoto, N;Nakayama, J;Arinami, T
脂肪细胞衍生的亮氨酸氨肽酶（阿拉普）在肾脏中灭活血管紧张素II和/或产生缓激肽，这表明阿拉普在血压调节中可能起作用。我们考虑了这样的假设，即阿拉普基因的基因组变异与高血压或血压的个体差异有关。我们在48名无关的日本个体中筛查了阿拉普基因的突变，并发现了33种多态性，其中包括15种新型多态性。然后，我们进行了两个阶段的分析。在第一阶段，在96名明显健康的个体中评估了8个错义多态性与血压的关联。在第二阶段中，只有最有希望的多态性与原发性高血压的143高血压和348正常血压受试者进行了评估。在八种错义多态性中，Ile 276 Met和Lys 528 Arg多态性与血压显着相关。随后的分析证实了Lys 528 Arg多态性与原发性高血压之间的关联。与Lys/Lys基因型相比，密码子528处Arg等位基因的存在对原发性高血压的估计比值比为2.3（P = 0.004）。这些发现支持阿拉普参与血压调节。2002年，《突变》19：251-257。(C)2002 Wiley-Liss，Inc.
Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two,stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight miss sense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure. Hum Mutat 19:251-257, 2002. (C) 2002 Wiley-Liss, Inc.