Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn's disease, in Canadian populations.
OBJECTIVE
A single-nucleotide polymorphism in the PTPN22 gene encoding the lymphoid protein tyrosine phosphatase (Lyp) has recently been identified as a functional variant associated with susceptibility to rheumatoid arthritis (RA), type 1 diabetes, and systemic lupus erythematosus. To determine whether association of this variant (PTPN22 1858T) with RA is reproducible and is also observed in another autoimmune condition, Crohn's disease, we investigated the association between the PTPN22 1858T allele and RA and Crohn's disease in a Canadian population.


METHODS
Two RA case-control cohorts representing a total of 1,234 patients and 791 healthy controls as well as a cohort of 455 patients with Crohn's disease and 190 controls were genotyped for the PTPN22 C1858T polymorphism, and genotype frequencies were compared between patients and controls.


RESULTS
Significant association of the PTPN22 1858T allele with RA was detected in both the Toronto-based RA cohort (P = 1.6 x 10(-6), odds ratio [OR] 1.8) and the Halifax-based RA cohort (P = 9.4 x 10(-4), OR 1.94). Association of the risk allele with RA was not affected by sex, age at disease onset, or the presence of either rheumatoid factor or rheumatoid nodules. No association between the PTPN22 risk allele and Crohn's disease was detected.


CONCLUSIONS
These observations confirm the association of RA susceptibility with the PTPN22 1858T allele. However, the data also reveal a lack of association between this variant and Crohn's disease, suggesting that the PTPN22 1858T allele is a risk allele for multiple, but not all, autoimmune diseases.
van Oene
Mark
M
Ellipsis Biotherapeutics Corporation, Toronto, Ontario, Canada.
Wintle
Richard F
RF
Liu
Xiangdong
X
Yazdanpanah
Mehrdad
M
Gu
Xiangjun
X
Newman
Bill
B
Kwan
Albert
A
Johnson
Benjamin
B
Owen
Julie
J
Greer
Wenda
W
Mosher
Dianne
D
Maksymowych
Walter
W
Keystone
Ed
E
Rubin
Laurence A
LA
Amos
Christopher I
CI
Siminovitch
Katherine A
KA
D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008221:Lymphoid Tissue / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases