Haplotype-based, case–control study of the receptor (calcitonin) activity-modifying protein (RAMP) 1gene in essential hypertension

The adrenomedullin receptor is a complex molecule that comprises the calcitonin-receptor-like receptor (CRLR) and the receptor-activity-modifying protein (RAMP). RAMP1 is a vasodilation factor, and RAMP1-deficient mice (RAMP1(−/−)) exhibit inflammatory responses with a significant transient increase in serum calcitonin-gene-related peptide levels and proinflammatory cytokines when compared with RAMP1(+/+) mice. The purpose of the present study was to investigate the relationships between essential hypertension (EH) and RAMP1gene single-nucleotide polymorphisms (SNPs) or haplotypes in a Japanese population via a case–control study. Based on a database search of the National Center of Biotechnology Information website and the HapMap project, we chose six RAMP1gene SNPs and performed an association study involving 263 patients with EH and 267 age-matched normotensive (NT) subjects. There was no significant difference between the EH and NT groups with regard to overall distribution of genotypes or SNP alleles. However, the haplotype-based case–control analysis revealed that there was a significant difference between the EH and NT groups with regard to overall distribution of the allele combinations at three SNPs—rs3754701–rs3769048–rs10199956—(P=0.002). The T-A-T haplotype was significantly more common in the EH group (10.3%) than in the NT control group (6.1%) (P=0.047). These results suggested that this T-A-T RAMP1gene haplotype might have utility as a genetic marker for EH and that the RAMP1gene or a neighbouring gene may be associated with increased susceptibility to EH.