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Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
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Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
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Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
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Journal Article
Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
2010
Overview
Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while 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 A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ2 test using Stata. Results Association to the CD40 gene was robustly replicated (p=2×10−4, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8×10−8, OR 0.87 (95% CI 0.83 to 0.92). Conclusion In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.
Publisher
BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited,BMJ Group
Subject
Arthritis, Rheumatoid - genetics
/ Arthritis, Rheumatoid - immunology
/ Biological and medical sciences
/ Clinical and Epidemiological Research
/ Cyclin-Dependent Kinase 6 - genetics
/ Diseases of the osteoarticular system
/ Female
/ Genes
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genotype
/ Humans
/ Male
/ Polymorphism, Single Nucleotide
/ R&D
/ Single-nucleotide polymorphism
/ Software
