Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus.
OBJECTIVE
To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).


METHODS
Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay.


RESULTS
The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]).


CONCLUSIONS
These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.
Orozco
Gisela
G
Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain.
Sánchez
Elena
E
González-Gay
Miguel A
MA
López-Nevot
Miguel A
MA
Torres
Belén
B
Cáliz
Rafael
R
Ortego-Centeno
Norberto
N
Jiménez-Alonso
Juan
J
Pascual-Salcedo
Dora
D
Balsa
Alejandro
A
de Pablo
Rosario
R
Nuñez-Roldan
Antonio
A
González-Escribano
Maria Francisca
MF
Martín
Javier
J
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D008221:Lymphoid Tissue / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000209:etiology; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D013941:Thymine
D003596:Cytosine; D010749:Phosphoprotein Phosphatases; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; D013941:Thymine