TRAF1–C5 as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study

• Published in: The New England journal of medicine Vol. 357; no. 12; pp. 1199 - 1209
• Main Authors: Plenge, Robert M, Seielstad, Mark, Padyukov, Leonid, Lee, Annette T, Remmers, Elaine F, Ding, Bo, Liew, Anthony, Khalili, Houman, Chandrasekaran, Alamelu, Davies, Leela R.L, Li, Wentian, Tan, Adrian K.S, Bonnard, Carine, Ong, Rick T.H, Thalamuthu, Anbupalam, Pettersson, Sven, Liu, Chunyu, Tian, Chao, Chen, Wei V, Carulli, John P, Beckman, Evan M, Altshuler, David, Alfredsson, Lars, Criswell, Lindsey A, Amos, Christopher I, Seldin, Michael F, Kastner, Daniel L, Klareskog, Lars, Gregersen, Peter K
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 20-09-2007
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoantibodies - blood; Biological and medical sciences; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 9 - genetics; Complement C5 - genetics; Disease; Epidemiology; Genealogy; General aspects; Genetic Predisposition to Disease; Genetics; Genomes; Genotype; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Linkage Disequilibrium; Logistic Models; Medical sciences; Medicin och hälsovetenskap; Peptides, Cyclic - immunology; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatases - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rheumatic diseases; Rheumatoid arthritis; Rheumatology; Risk Factors; Sequence Analysis, DNA; TNF Receptor-Associated Factor 1 - genetics; Sweden; Medicine; Immunopathology; Chronic; Rheumatoid arthritis; Diseases of the osteoarticular system; Risk factor; Autoimmune disease; Risk; Inflammatory joint disease; Locus; Epidemiology
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa073491

A genomewide association study of North American and Swedish patients with rheumatoid arthritis who were seropositive for autoantibodies against cyclic citrullinated peptide yielded susceptibility variants in the usual suspects:
HLA-DRB1
and
PTPN22
. A new locus was also implicated: a SNP that lies between the
TRAF1
and
C5
genes.
A genomewide association study of North Americans and Swedes with rheumatoid arthritis yielded susceptibility variants in the usual suspects:
HLA-DRB1
and
PTPN22
. A new locus was also implicated: a SNP that lies between the
TRAF1
and
C5
genes.
Rheumatoid arthritis is a common inflammatory arthritis of unknown cause, in which both genetic and environmental risk factors have been implicated.
1
–
3
The genetic contribution to a susceptibility to rheumatoid arthritis has been shown in studies of twins
4
and families
5
and in genomewide linkage scans.
6
–
11
Two genes have shown a strong association with susceptibility:
PTPN22
12
,
13
and
HLA-DRB1
.
14
Variants of each gene elevate the risk primarily for a subgroup of severe rheumatoid arthritis characterized by the presence of autoantibodies against cyclic citrullinated peptide (anti–CCP-positive).
12
,
15
,
16
We have recently reported a significant association at
STAT4
on chromosome 2q. . . .