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.
Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Chieko
C
Kyogoku
Carl D
CD
Langefeld
Ward A
WA
Ortmann
Annette
A
Lee
Scott
S
Selby
Victoria E H
VE
Carlton
Monica
M
Chang
Paula
P
Ramos
Emily C
EC
Baechler
Franak M
FM
Batliwalla
Jill
J
Novitzke
Adrienne H
AH
Williams
Clarence
C
Gillett
Peter
P
Rodine
Robert R
RR
Graham
Kristin G
KG
Ardlie
Patrick M
PM
Gaffney
Kathy L
KL
Moser
Michelle
M
Petri
Ann B
AB
Begovich
Peter K
PK
Gregersen
Timothy W
TW
Behrens
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