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.
Assuntos
Artrite Reumatoide/genética , Marcadores Genéticos , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The objective of this study was to determine the association of the CD40LG 3'-UTR (CA)n microsatellite with rheumatoid arthritis (RA) and CD40LG mRNA levels in females from western Mexico. A case-control study with 219 RA patients and 175 control subjects (CS) was conducted. Genotyping was performed by polymerase chain reaction (PCR), X 2 test was used to compare genotype and allele frequencies, and odds ratios and 95% confidence intervals were calculated to evaluate the association between RA and the microsatellite. CD40LG mRNA expression was assessed by real-time quantitative PCR. For comparisons between groups, Kruskal-Wallis or Mann-Whitney U tests for non-parametric data and ANOVA test for parametric data were performed. Among the 13 different alleles identified, CA25 was the most represented (45.4% RA and 46.3% CS). Stratification according to CA repeats as