期刊
NATURE GENETICS
卷 41, 期 7, 页码 820-U77出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.395
关键词
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资金
- US National Institutes of Health [NO1-AR-2-2263, RO1 AR44422]
- Eileen Ludwig Greenland Center for Rheumatoid Arthritis and the Muriel Fusfeld Foundation
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Canadian Institutes for Health Research [MOP79321]
- Ontario Research Fund [RE01061]
- Canada Research Chair
We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 x 10(-10)). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR 1.25 (P = 3.08 x 10(-14)) for marker rs13031237 and an allelic OR 1.21 (P = 2.60 x 10(-11)) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 x 10(-9)) and BLK (rs2736340; OR = 1.19; P = 5.69 x 10(-9)). c-Rel is an NF-kappa B family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ(1,2).
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