Haplotype-based case–control study of receptor (calcitonin) activity-modifying protein-1 gene in cerebral infarction

Calcitonin gene-related peptide (CGRP) receptor is a complex molecule that consists of calcitonin receptor-like receptor and receptor activity-modifying protein-1 (RAMP1). It was recently reported that RAMP1-deficient mice (RAMP1(−/−)) showed inflammatory responses with a transiently significant increase in serum CGRP levels and proinflammatory cytokines when compared with RAMP1(+/+) mice. The aim of this study was to investigate the relationship between the human RAMP1 gene and cerebral infarction (CI) using single-nucleotide polymorphisms (SNPs) in a Japanese population. We selected six SNPs in the human RAMP1 gene (rs3754701, rs3769048, rs7557078, rs1584243, rs10199956 and rs7590387) and performed a case–control study using each SNP and haplotype in 171 CI patients and 234 controls. There were no significant differences in overall distribution of genotype and allele frequencies of the SNPs between the CI and control groups. However, there was a significant difference in overall distribution between the CI and control groups (P<0.001) in the haplotype-based case–control study with the combinations of rs3754701–rs3769048–rs7590387. The T-A-C susceptibility haplotype for CI was significantly more frequent than in the control group (P=0.0024). The results suggest that the T-A-C haplotype is a genetic marker for CI, and that RAMP1 or neighbouring genes are associated with increased susceptibility to CI.