Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus.
OBJECTIVE
The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE.


METHODS
A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses.


RESULTS
In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi2= 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi2= 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators.


CONCLUSIONS
The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports.
Kaufman
Kenneth M
KM
Oklahoma Medical Research Foundation, and Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA.
Kelly
Jennifer A
JA
Herring
Billy J
BJ
Adler
Adam J
AJ
Glenn
Stuart B
SB
Namjou
Bahram
B
Frank
Summer G
SG
Dawson
Sarah L
SL
Bruner
Gail R
GR
James
Judith A
JA
Harley
John B
JB
D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D009825:Oklahoma / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000208:ethnology
C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases