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Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study.
Orozco, GG, Eyre, SS, Hinks, AM, Ke, X, Wellcome Trust Case Control Consortium, YEAR Consortium, Wilson, A, Bax, D, Morgan, A, Emery, P, Steer, S, Hocking, L, Reid, D, Wordsworth, P, Harrison, P, Thomson, W, Barton, A, Worthington, J
Annals of the Rheumatic Diseases. 2010;69(5):813-816.
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Abstract
OBJECTIVE: A recent meta-analysis of published genome wide association studies (GWASs) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with RA susceptibility whilst a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: Four SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3,962 UK RA cases and 3,531 healthy controls using the Sequenom iPlex platform. Genotype counts in cases and controls were analysed using the chi squared test using Stata. RESULTS: Association to the CD40 gene was robustly replicated [P= 2 x 10-4, OR (95% CI) 0.86 (0.79-0.93)] and we found modest evidence for association to the CCL21 locus [P= 0.04, OR (95% CI) 1.08 (1.01-1.16)]. However, we found no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in our UK population. Following a meta-analysis including the original data, association to CD40 was confirmed [P= 7.8 x 10-8, OR (95% CI) 0.87 (0.83-0.92)]. CONCLUSION: In this large UK cohort, we have found strong association of the CD40 gene with susceptibility to RA, and weaker evidence for association with RA in the CCL21 locus.