The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis

• Authors: Maria I. Danila, University of Alabama at Birmingham; Andrew O. Westfall, University of Alabama at Birmingham; Krishnan Raman, University of Alabama at Birmingham; Lang Chen, University of Alabama at Birmingham; Richard J. Reynolds, University of Alabama at Birmingham; Laura B. Hughes, University of Alabama at Birmingham; Donna K. Arnett, University of Alabama at Birmingham; Gerald McGwin, University of Alabama at Birmingham; Alexander J. Szalai, University of Alabama at Birmingham; Désirée M. van der Heijde, Leiden University Medical Center; Doyt Conn, Emory University; Leigh F. Callahan, University of North Carolina at Chapel Hill; Larry W. Moreland, University of Pittsburgh; S. Louis Bridges, Jr, University of Alabama at Birmingham
• Journal Title: Genes and Immunity
• Volume: Volume 16, Number 7
• Publisher: Nature Publishing Group | 2015-10-01, Pages 446-451
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/gene.2015.24
• Subjects: Health Sciences, Immunology; Biology, Genetics
• Keywords: Genetics & Heredity; Immunology; SINGLE NUCLEOTIDE POLYMORPHISMS; JOINT DESTRUCTION; PROMOTER POLYMORPHISM; SHARED EPITOPE; C reactive protein; genetics; rheumatoid arthritis; joint damage; radiography

Abstract

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.