Association study of calcitonin-receptor-like receptor gene in essential hypertension

• Published in: American journal of hypertension Vol. 18; no. 3; pp. 403 - 408
• Main Authors: Sano, Morihiko, Kuroi, Nobuhiro, Nakayama, Tomohiro, Sato, Naoyuki, Izumi, Yoichi, Soma, Masayoshi, Kokubun, Shinichiro
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2005; Oxford University Press; Elsevier Science
• Subjects: Adult; Arterial hypertension. Arterial hypotension; association study; Biological and medical sciences; Blood and lymphatic vessels; Calcitonin Receptor-Like Protein; calcitonin-receptor-like receptor; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Essential hypertension; Experimental diseases; Female; Genetic Markers; Genotype; Humans; Hypertension - epidemiology; Hypertension - genetics; Logistic Models; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Prevalence; Receptors, Calcitonin - genetics; Sex Distribution; single-nucleotide polymorphism; Essential hypertension; calcitonin-receptor-like receptor; single-nucleotide polymorphism; association study; Hypertension; Calcitonin; Thyroid hormone; Cardiovascular disease; Polymorphism
• ISSN: 0895-7061; 1879-1905; 1941-7225
• 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.