Sato Mikano, Nakayama Tomohiro, Soma Masayoshi, Aoi Noriko, Kosuge Kotoko, Haketa Akira, Izumi Yoichi, Matsumoto Koichi, Sato Naoyuki, Kokubun Shinichiro
Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
Prostaglandins Leukot Essent Fatty Acids. 2007 Jul;77(1):15-20. doi: 10.1016/j.plefa.2007.04.004. Epub 2007 Jul 20.
Essential hypertension (EH) is a complex multifactorial polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. In the kidney, prostaglandins (PGs) are important mediators of vascular tone and salt and water homeostasis, and are involved in the mediation and/or modulation of hormonal action. In previous studies, mice deficient in the prostaglandin E2 (PGE(2)) EP2 receptor had resting systolic blood pressure (BP) that was significantly lower than that of wild-type controls. The BP of those mice increased when they were put on a high-salt diet, suggesting that the EP2 receptor is involved in sodium handling by the kidney. In the present study, we investigated the association between EH and nucleotide polymorphisms in the gene encoding the prostaglandin E2 receptor subtype EP2 (PTGER2).
We selected three single-nucleotide polymorphisms (SNP) in the human PTGER2 gene (rs1254601, rs2075797, and rs17197), and we performed a genetic association study of 266 EH patients and 253 age-matched normotensive (NT) controls.
There was no significant difference in overall distribution of genotypes or alleles of any of the SNP between the EH and NT groups. However, among men, the A/A type of the SNP rs17197 (rs17197, A/G in 3'UTR) was significantly more frequent in EH subjects than in NT subjects (P=0.041).
The present findings suggest that rs17197 is useful as a genetic marker of EH in men.
原发性高血压（EH）是一种复杂的多因素多基因疾病，被认为是个体基因组成与各种环境因素相互作用的结果。在肾脏中，前列腺素（PGs）是血管张力以及盐和水平衡的重要介质，并参与激素作用的介导和/或调节。在先前的研究中，前列腺素E2（PGE(2)）EP2受体缺陷的小鼠静息收缩压（BP）显著低于野生型对照。当给这些小鼠喂食高盐饮食时，它们的血压升高，这表明EP2受体参与肾脏对钠的处理。在本研究中，我们调查了原发性高血压与前列腺素E2受体亚型EP2（PTGER2）编码基因中的核苷酸多态性之间的关联。
我们在人类PTGER2基因中选择了三个单核苷酸多态性（SNP）（rs1254601、rs2075797和rs17197），并对266例EH患者和253例年龄匹配的血压正常（NT）对照进行了基因关联研究。
EH组和NT组之间任何SNP的基因型或等位基因的总体分布均无显著差异。然而，在男性中，SNP rs17197（rs17197，3'UTR中的A/G）的A/A型在EH受试者中比在NT受试者中显著更常见（P = 0.041）。
本研究结果表明，rs17197可作为男性EH的遗传标记。
