RESUMO
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by lymphocytic infiltration, glandular dysfunction and systemic manifestations. Lyp protein is a negative regulator of the T cell receptor encoded by the tyrosine phosphatase nonreceptor-type 22 (PTPN22) gene. Multiple single-nucleotide polymorphisms (SNPs) in the PTPN22 gene have been associated with susceptibility to autoimmune diseases. This study aimed to investigate the association of PTPN22 SNPs rs2488457 (-1123 G>C), rs33996649 (+788 G>A), rs2476601 (+1858 C>T) with pSS susceptibility in Mexican mestizo subjects. METHODS: One hundred fifty pSS patients and 180 healthy controls (HCs) were included. Genotypes of PTPN22 SNPs were identified by PCR-RFLP. PTPN22 expression was evaluated through RT-PCR analysis. Serum anti-SSA/Ro and anti-SSB/La levels were measured using an ELISA kit. RESULTS: Allele and genotype frequencies for all SNPs studied were similar in both groups (p > 0.05). pSS patients showed 17-fold higher expression of PTNP22 than HCs, and mRNA levels correlated with SSDAI score (r2 = 0.499, p = 0.008) and levels of anti-SSA/Ro and anti-SSB/La autoantibodies (r2 = 0.200, p = 0.03 and r2 = 0.175, p = 0.04, respectively). Positive anti-SSA/Ro pSS patients expressed higher PTPN22 mRNA levels (p = 0.008), with high focus scores by histopathology (p = 0.02). Moreover, PTPN22 expression had high diagnostic accuracy in pSS patients, with an AUC = 0.985. CONCLUSIONS: Our findings demonstrate that the PTPN22 SNPs rs2488457 (-1123 G>C), rs33996649 (+788 G>A) and rs2476601 (+1858 C>T) are not associated with the disease susceptibility in the western Mexican population. Additionally, PTPN22 expression may be helpful as a diagnostic biomarker in pSS.
RESUMO
PTPN22 represents an important non-HLA gene that has been strongly associated with rheumatoid arthritis (RA) pathogenesis. Several studies have reported a specific genetic variant for PTPN22 (+788 G>A; rs33996649) that might be associated with decreased RA risk in Caucasian population; nevertheless, its specific role in western Mexican population has not been yet described. A case-control study with 443 RA patients and 317 control subjects (CS) was conducted. The genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique and the PTPN22 mRNA expression was determined by SYBR Green-based real-time quantitative-PCR assay. No association between the PTPN22 +788 G>A polymorphism and RA susceptibility in western Mexican population was found when comparing genotype and allelic frequencies between RA patients and CS (G/G vs. G/A: OR 0.55, p = 0.14, 95% CI 0.22-1.32; G vs. A: OR 0.56, p = 0.14, 95% CI 0.23-1.36). The PTPN22 mRNA expression increased 4.6-fold more in RA patients than in CS, and RA patients, carriers of PTPN22 +788 G/A genotype, expressed 15.6-fold more than RA patients carrying the homozygous G/G genotype. Overall, these results showed that the PTPN22 +788 G>A polymorphism is not associated with RA susceptibility in western Mexican population, whereas the presence of G/A genotype is associated with increased PTPN22 mRNA expression in RA patients.