Rs2476601

This SNP, located in the PTPN22 gene and also known as R620W, or 1858C>T, may influence Rheumatoid Arthritis and other autoimmune diseases, including but not limited to, multiple sclerosis, Crohn's disease, celiac disease and type-1 diabetes.

In an expanded follow-up study of >6,000 controls and 6,000 patients, the heterozygote odds ratio for type-1 diabetes for this SNP was recalculated to be 1.98 (CI 1.82-2.15).

rs2476601 was confirmed in another 2007 study to be a risk factor for RA.


 * confirms the association of rs2476601 rheumatoid arthritis
 * two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA
 * see rs2476601(A;G)

rs2476601 shows a 0.75 (r squared) correlation with rs6679677, a SNP in the RSBN1 gene associated with rheumatoid arthritis.

associations of rs2476601 in PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals.

studied ~300 UK patients with Behcet's disease and found that the R620W allele (i.e. rs2476601(A)) appeared to provide protection from Behcet's disease. The odds ratio for protection was calculated to be 2.4 (CI: 1.2 - 4.7).

1858T allele had an allelic odds ratio (OR) of 2.16 for generalized vitiligo and a genotypic OR of 2.35 as C/T heterozygotes. Similarly, individuals carrying the PTPN22 1858T allele had an allelic OR of 2.05 for the expanded autoimmunity phenotype, and a genotypic OR of 2.19 for C/T heterozygotes.

] Confirms association of rs2476601 with type-1 diabetes in a Sardinian population of 490 sporadic patients (794 families).

In study of 332 Norwegian patients plus a meta-analysis, the rs2476601(A) allele was linked to autoimmune Addison's disease (p=0.003)

rs2476601(A) has a higher relative risk in type-1 diabetes cases carrying lower risk HLA class II genotypes than in those carrying higher risk ones (p=1.36x10-4 in a test of interaction).

] rs2476601 is not associated with Graves' disease in a study of Japanese patients.

rs2476601(A) allele is associated with (slightly) increased risk for systemic sclerosis in European Caucasians.

23andMe blog rs2476601(A) increases the risk of type 1 diabetes and rheumatoid arthritis, but has shown to be protective for Crohn's disease.

Women with (T;T) and (C;T) genotypes displayed a 2x increased risk of systemic lupus erythematosus (95% CI=1.324 - 3.070, P=0.0014)

No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey.

Meta-analysis across 12 studies, totaling 4,300+ patients, concludes that there is an association between the rs2476601(A) allele and risk for systemic sclerosis, with an odds ratio of 1.169 (CI: 1.05 - 1.3, p = 0.004).

Promethease reports for rs2476601 from Trait-o-matic are consistently finding this called as (A;G), while microarray results seem to follow the HapMap predictions. The source of this originates upstream in several different genotype callers:
 * maq
 * SoapSNP
 * AB_SOLiD_SNP_caller
 * JW
 * NA18507
 * SIQ2
 * CV
 * GSNAP

This is probably triggered by the oddness of this dbSNP entry in which it is a C=>T in NM_012411.2 and a T=>C in NM_015967.3 and/or the fact NT_019273.18 was replaced by NT_032977

Hashimoto's Thyroiditis