Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
We genotyped 525 independent North American white individuals with systemic lupus erythematosus (SLE) for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 white control individuals. The R620W SNP was associated with SLE (genotypic P=.00009), with estimated minor (T) allele frequencies of 12.67% in SLE cases and 8.64% in controls. A single copy of the T allele (W620) increases risk of SLE (odds ratio [OR]=1.37; 95% confidence interval [CI] 1.07-1.75), and two copies of the allele more than double this risk (OR=4.37; 95% CI 1.98-9.65). Together with recent evidence showing association of this SNP with type 1 diabetes and rheumatoid arthritis, these data provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity.
Kyogoku
Chieko
C
Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Langefeld
Carl D
CD
Ortmann
Ward A
WA
Lee
Annette
A
Selby
Scott
S
Carlton
Victoria E H
VE
Chang
Monica
M
Ramos
Paula
P
Baechler
Emily C
EC
Batliwalla
Franak M
FM
Novitzke
Jill
J
Williams
Adrienne H
AH
Gillett
Clarence
C
Rodine
Peter
P
Graham
Robert R
RR
Ardlie
Kristin G
KG
Gaffney
Patrick M
PM
Moser
Kathy L
KL
Petri
Michelle
M
Begovich
Ann B
AB
Gregersen
Peter K
PK
Behrens
Timothy W
TW
D000483:Alleles; D018450:Disease Progression; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D009656:North America; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D044465:White People
D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases