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The objective of this study was to clarify relationships between the C-reactive protein (CRP) gene and both the serum level of CRP and arterial pulse wave velocity (PWV), using haplotype analysis of healthy elderly Japanese. Five single-nucleotide polymorphisms (SNPs) of the human CRP gene (rs1341665, rs3091244, rs1800947, rs1130864 and rs1205) were used to genotype 315 healthy elderly Japanese subjects (mean age, 77.9 +/- 4.1 years; male/female ratio, 0.96). Linkage disequilibrium was analyzed for the five SNPs. The frequency of each haplotype and diplotype was estimated using the expectation/maximization (EM) algorithm. There were statistically significant associations between the CRP level and two CRP genotypes; the p value for the T allele of rs3091244 (CT + AT + TT vs. CC + CA + AA) was 0.002 (95% confidential interval [CI], 2.1-24), and the p value for the T allele of rs1130864 (TT + TC vs. CC) was 0.002 (95% CI, 2.1-24). The only genotype that was significantly associated with arterial PWV was the C allele of rs1800947, with a p value of 0.039. The haplotype was constructed using rs1341665, rs3091244 and rs1800947, in that order. There was a significant association between the CRP level and the T-T-G haplotype, with a p value of 0.002 (95% CI, 2.1-24). There was a significant association between arterial PWV and the C-C-C haplotype, with a p value of 0.039. We concluded that rs3091244, rs1130864 and the T-T-G haplotype are genetic markers for elevated basal CRP levels. rs1800947 and the C-C-C haplotype appear to be susceptibility markers for atherosclerosis, but this requires confirmation.

Polymorphism of the C-Reactive Protein (CRP) Gene Is Related to Serum CRP Level and Arterial Pulse Wave Velocity in Healthy Elderly Japanese