Rs2476601

From SNPedia

GWAS snp
PMID	[PMID 18587394]
Trait	Crohn's disease
Title	Genome-wide assocation defines more than 30 distinct susceptibility loci for Crohn's disease
Risk Allele	G
P-val	1E-8
Odds Ratio	1.31 [NR]

GWAS snp
PMID	[PMID 17632545]
Trait	Type 1 diabetes
Title	A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene
Risk Allele	A
P-val	9.9999999999999995E-8
Odds Ratio	1.80 [1.44-2.24]

GWAS snp
PMID	[PMID 19430480]
Trait	Type 1 diabetes
Title	Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
Risk Allele
P-val	9E-85
Odds Ratio	NR NR

GWAS snp
PMID	[PMID 19503088]
Trait	Rheumatoid arthritis
Title	REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis
Risk Allele
P-val	2E-21
Odds Ratio	NR NR

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). [PMID 17554260]

rs2476601 was confirmed in another 2007 study to be a risk factor for RA [PMID 17804836].

• [PMID 16490755] confirms the association of rs2476601 rheumatoid arthritis
• [PMID 15674368] two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA
• [PMID 15719322] see rs2476601(A;G)
• [PMID 15934099]
• [PMID 16052172]
• [PMID 16175503]
• [PMID 16185327]
• [PMID 16470599]

rs2476601 shows a 0.75 (r squared) correlation with rs6679677, a SNP in the RSBN1 gene associated with rheumatoid arthritis. [PMID 17554300]

[PMID 17133608] 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.

[PMID 17660222] 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).

[PMID 18200060] 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.

[PMID 17934143]] Confirms association of rs2476601 with type-1 diabetes in a Sardinian population of 490 sporadic patients (794 families).

[PMID 18301444] In study of 332 Norwegian patients plus a meta-analysis, the rs2476601(A) allele was linked to autoimmune Addison's disease (p=0.003)

[PMID 18305142] 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).

[PMID 18578611]] rs2476601 is not associated with Graves' disease in a study of Japanese patients.

[PMID 18576360] rs2476601(A) allele is associated with (slightly) increased risk for systemic sclerosis in European Caucasians.

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

[PMID 19210878] 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)

[PMID 19357851] No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey.

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

[PMID 19780033] Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Meniere's disease

[PMID 19956106] Analysis of 19 genes for association with type I diabetes in the Type I Diabetes Genetics Consortium families

[PMID 19956096] rs2476601 T allele (R620W) defines high-risk PTPN22 type I diabetes-associated haplotypes with preliminary evidence for an additional protective haplotype

[PMID 20032229] Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms

[PMID 19951419] Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis

GWAS snp
PMID	[PMID 20410501]
Trait	Vitiligo
Title	Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo
Risk Allele	A
P-val	1E-7
Odds Ratio	1.39 [1.23-1.57]

[PMID 20522204] PTPN22 gene regulates natural killer cell proliferation during in vitro expansion

GWAS snp
PMID	[PMID 20453842]
Trait	Rheumatoid arthritis
Title	Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock
Risk Allele	A
P-val	9E-74
Odds Ratio	1.94 [1.81-2.08]

[PMID 20615141] Association of the Protein Tyrosine Phosphatase Nonreceptor 22 Haplotypes with Autoimmune Thyroid Disease in the Japanese Population

[PMID 20498205] Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers