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Objective  The gene coding for C-reactive protein (CRP) is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Recently, 2 single-nucleotide polymorphisms (SNP) in the  CRP  gene (+838, +2043) have been shown to be associated with CRP concentrations and/or SLE risk in a British family-based cohort. Our study was done to confirm the reported association in an independent population-based case-control cohort, and also to investigate the influence of 3 additional  CRP  tagSNP (−861, −390, +90) on SLE risk and serum CRP concentrations.    Methods  DNA from 337 Caucasian women who met the American College of Rheumatology criteria for definite (n = 324) or probable (n = 13) SLE and 448 Caucasian healthy female controls was genotyped for 5  CRP  tagSNP (−861, −390, +90, +838, +2043). Genotyping was performed using restriction fragment length polymorphism-polymerase chain reaction, pyrosequencing, or TaqMan assays. Serum CRP levels were measured using ELISA. Association studies were performed using the chi-squared distribution, Z-test, Fisher’s exact test, and analysis of variance. Haplotype analysis was performed using EH software and the haplo.stats package in R 2.1.2.    Results  While none of the SNP were found to be associated with SLE risk individually, there was an association with the 5 SNP haplotypes (p &lt; 0.001). Three SNP (−861, −390, +90) were found to significantly influence serum CRP level in SLE cases, both independently and as haplotypes.    Conclusion  Our data suggest that unique haplotype combinations in the  CRP  gene may modify the risk of developing SLE and influence circulating CRP levels.

Genetic Variation in C-Reactive Protein (CRP) Gene May Be Associated with Risk of Systemic Lupus Erythematosus and CRP Concentrations