Sano Morihiko, Kuroi Nobuhiro, Nakayama Tomohiro, Sato Naoyuki, Izumi Yoichi, Soma Masayoshi, Kokubun Shinichiro
Nihon University School of Medicine, Advanced Medical Research Center, Nihon University School of Medicine, Ooyaguchi-kamimachi, 30-1 Itabashi-ku, Tokyo, Japan.
Am J Hypertens. 2005 Mar;18(3):403-8. doi: 10.1016/j.amjhyper.2004.10.016.
Plasma adrenomedullin (ADM) concentrations increase in patients with hypertension, renal failure, heart failure, essential pulmonary hypertension, myocardial infarction, endotoxin shock, and many other conditions. The ADM receptor is a complex molecule that consists of calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2). Because CRLR determines the binding specificity of ADM, the CRLR gene is thought to be a susceptibility gene of hypertension. However, studies have not yet defined the relationship between the CRLR gene and hypertension. The aim of the present study was to investigate relationships between single-nucleotide polymorphisms (SNP) in the human CRLR gene and essential hypertension (EH) in a Japanese population.
We selected four SNP in the human CRLR gene (rs3771073, rs696574, rs698590, and rs1528233), and we performed a genetic association study in 209 EH patients and 216 age-matched normotensive (NT) individuals.
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 women, the T allele of the SNP rs696574 (C --> T, in intron 6) was significantly more frequent in EH subjects than in NT subjects (P = .032).
Our findings suggest that rs696574 can be used as a genetic marker of EH in women.
高血压、肾衰竭、心力衰竭、特发性肺动脉高压、心肌梗死、内毒素休克及许多其他病症患者的血浆肾上腺髓质素(ADM)浓度会升高。ADM受体是一种复杂分子,由降钙素受体样受体(CRLR)和受体活性修饰蛋白2(RAMP2)组成。由于CRLR决定ADM的结合特异性,因此CRLR基因被认为是高血压的易感基因。然而,研究尚未明确CRLR基因与高血压之间的关系。本研究的目的是调查日本人群中人类CRLR基因单核苷酸多态性(SNP)与原发性高血压(EH)之间的关系。
我们在人类CRLR基因中选择了4个SNP(rs3771073、rs696574、rs698590和rs1528233),并在209例EH患者和216例年龄匹配的血压正常(NT)个体中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,在女性中,SNP rs696574(第6内含子中的C→T)的T等位基因在EH受试者中比在NT受试者中显著更常见(P = 0.032)。
我们的研究结果表明,rs696574可作为女性EH的遗传标记。