Abstract
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 < 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.
Key Indexing Terms:Footnotes
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P.B. Shih, PhD, Department of Human Genetics; S. Manzi, MD, MPH; P. Shaw, RN, Division of Rheumatology and Clinical Immunology; M. Kenney, MS, Department of Human Genetics; A.H. Kao, MD, MPH, Division of Rheumatology and Clinical Immunology; F. Bontempo, MD, Department of Medicine; M.M. Barmada, PhD; C. Kammerer, PhD; M.I. Kamboh, PhD, Department of Human Genetics.
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Supported in part by the National Heart, Lung, and Blood Institute Grants HL074165 and HL54900, the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grants AR46588 and AR002213, and a grant from the National Institutes of Health General Clinical Research Center M01-RR000056.
- Accepted for publication June 3, 2008.
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