Association between C-reactive protein gene haplotypes and C-reactive protein levels in Taiwanese: Interaction with obesity

Objective: The level of C-reactive protein (CRP), an inflammatory marker that predicts future cardiovascular events, is a heritable trait. Our aim was to test the statistical associations between variations in the CRP gene and serum CRP levels in a Taiwanese population with interaction analysis. Methods: A sample population of 617 Taiwanese subjects was enrolled. Five CRP single nucleotide polymorphisms (SNPs) previously reported to be associated with CRP level and with reasonable coverage of the CRP gene region were analyzed using polymerase chain reaction and restriction enzyme digestion or by TaqMan SNP Genotyping Assays. Results: After adjusting for clinical covariates, minor alleles of 3 of the 5 SNPs were associated with change in CRP level: rs3091244 and rs1205 were associated with increased CRP level (P = 0.001 and P < 0.001, respectively) and rs1800947 with decreased CRP level (P = 0.003). Two haplotypes inferred from 5 SNPs (GCGCG and AAGCG) were associated with increased CRP level (P = 0.017 and P < 0.0001, respectively). Interaction analysis revealed interaction of obesity with CRP genotypes associated with high CRP level (interaction P = 0.034 and 0.020 for SNPs rs2794521 and rs1800947, respectively). An effect of obesity on CRP level was also noted in haplotype interaction analysis with the association occurring predominantly in obese subjects (P = 0.034). Conclusion: CRP polymorphisms are independently associated with increased or decreased CRP level in Taiwanese. Further, CRP genotypes/haplotypes interact with obesity to set CRP level. These findings have implications for the prediction of atherosclerotic disease.