P2RY2 has an important function in the regulation of blood pressure by activating adenosine triphosphate (ATP). The aim of this study was to investigate the association between the human P2RY2 gene and essential hypertension (EH) through a haplotype-based casecontrol study that included two gender groups. The 273 EH patients and 255 age-matched controls were genotyped for five single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936 and rs10898909). Data were analysed for men and women separately and then as a combined total group. For the total and the men only groups, the genotype distribution of the T allele of rs4944831 and the recessive model (GG vs TG þ TT) of rs4944831 differed significantly between the EH patients and controls (P ¼ 0.028 and 0.019; P ¼ 0.009 and 0.008, respectively). Logistic regression showed that for the total and men groups, the TG þ TT genotype of rs4944831 was more prevalent in EH patients than in the controls (P ¼ 0.026 and 0.011, respectively). For men, the overall distribution of the haplotype (SNP2-SNP4-SNP5) was significantly different between the EH patients and the controls (P ¼ 0.006). As compared with controls, the frequency of the T-A-G haplotype was significantly higher, whereas the T-C-G haplotype was significantly lower for the EH patients (P ¼ 0.001 and 0.014, respectively). In conclusion, the present results indicate that rs4944831 and the T-A-G haplotype of the human P2RY2 gene might be genetic markers for EH in Japanese men.
Calcitonin gene-related peptide (CGRP) receptor is a complex molecule that consists of calcitonin receptorlike receptor and receptor activity-modifying protein-1 (RAMP1). It was recently reported that RAMP1-deficient mice (RAMP1(À/À)) showed inflammatory responses with a transiently significant increase in serum CGRP levels and proinflammatory cytokines when compared with RAMP1( þ / þ ) mice. The aim of this study was to investigate the relationship between the human RAMP1 gene and cerebral infarction (CI) using singlenucleotide 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 casecontrol 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 (Po0.001) 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 ¼ 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.
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 RAMP1 gene 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 RAMP1 gene 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 RAMP1 gene haplotype might have utility as a genetic marker for EH and that the RAMP1 gene or a neighbouring gene may be associated with increased susceptibility to EH.
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