Relationships between C-reactive protein concentration and genotype in healthy volunteers

Background: Polymorphisms of the gene for C-reactive protein (CRP) alter baseline serum CRP concentrations. The impact of polymorphisms of the CRP gene (genotype) on the normal range for CRP concentrations (phenotype) has not been determined. This study evaluated the median serum CRP concentrations in normal subjects stratified for CRP genotype, after adjustment for relevant covariates as well as polymorphisms in tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) genotypes. Methods: A total of 423 healthy adults without infectious or inflammatory conditions undergoing phlebotomy for laboratory testing were enrolled in the study. Assays for serum high sensitivity CRP (hsCRP), IL-6, and TNF-alpha genotypes were measured. Results: The median hs-CRP concentration was 0.96 mg/L (range-0.1-40.15 mg/L). The CRP 1444 C/T heterozygote and homozygote genotype was associated with a significantly higher hs-CRP concentration (p < 0.05), even after multivariate analysis controlling for age, gender, body mass index, hypertension, dyslipidemia and obstructive sleep apnea. The CRP 286 C/T/A heterozygote genotype was significant (p < 0.05) in the multi-variable analysis, univariately was borderline significant (p = 0.052). Conclusions: Selected genetic polymorphisms of the CRP gene are independently associated with higher basal hs-CRP concentrations in healthy adults. Larger studies are needed to perform haplotype analyses and to adequately evaluate the relationship between hs-CRP and genetic polymorphisms with lower allelic frequencies.