Analysis of -1123 G>C, +788 G>A and +1858 C>T Polymorphisms in Patients with Primary Sjögren's Syndrome.

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 () gene. Multiple single-nucleotide polymorphisms (SNPs) in the gene have been associated with susceptibility to autoimmune diseases. This study aimed to investigate the association of 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 SNPs were identified by PCR-RFLP. 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 ( > 0.05). pSS patients showed 17-fold higher expression of than HCs, and mRNA levels correlated with SSDAI score ( = 0.499, = 0.008) and levels of anti-SSA/Ro and anti-SSB/La autoantibodies ( = 0.200, = 0.03 and = 0.175, = 0.04, respectively). Positive anti-SSA/Ro pSS patients expressed higher mRNA levels ( = 0.008), with high focus scores by histopathology ( = 0.02). Moreover, expression had high diagnostic accuracy in pSS patients, with an AUC = 0.985.

CONCLUSIONS

Our findings demonstrate that the 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, expression may be helpful as a diagnostic biomarker in pSS.