ABSTRACT
STAT4 has been consistently associated with several autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The aim of this study was to determine whether the STAT4 rs7574865G/T polymorphism confers susceptibility for RA and SLE in a sample of Mexican patients. This study included 869 individuals: 415 patients with RA, 128 patients with SLE, and 326 controls. Genotyping using TaqMan probes showed an association between the STAT4 rs7574865G/T polymorphism and RA (GG vs. TT: OR 1.99, p=0.0009; G vs. T: OR 1.42, p=0.0009) and SLE (GG vs. TT: OR 2.98, 0.0003; G vs. T: OR 1.74, p=0.0002). Gender stratification showed an association with RA (GG vs. TT: OR 1.99, 95% CI 1.3-3.1, p=0.002; G vs. T: OR 1.42, 95% CI 1.1-1.8, p=0.002) and SLE (GG vs. TT: OR 3.3, 95% CI 1.7-6.2, p=0.0002; G vs. T: OR 1.8, 95% CI 1.3-2.4, p=0.0002) in women. Thus, the STAT4 rs7574865G/T polymorphism confers risk for RA and SLE in the Mexican population.
Subject(s)
Arthritis, Rheumatoid/genetics , Lupus Erythematosus, Systemic/genetics , STAT4 Transcription Factor/genetics , Adult , Arthritis, Rheumatoid/epidemiology , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Genotype , Humans , Lupus Erythematosus, Systemic/epidemiology , Male , Mexico/epidemiology , Middle Aged , Polymorphism, Single Nucleotide , Risk , Sex FactorsABSTRACT
Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.
Subject(s)
Arthritis, Rheumatoid/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Receptors, Immunologic/genetics , Trans-Activators/genetics , Adult , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Mexico/epidemiology , Middle Aged , Phenotype , Risk FactorsABSTRACT
A large number of diseases occur in association with specific HLA-B or -C alleles. Recently a new gene, termed major histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown, but, it is structurally related to HLA class I genes, is polymorphic, and is potentially associated with several diseases. Some DNA-based techniques have previously been described to type for MICA including sequencing and single-strand conformational polymorphism. In this paper we describe the application of sequence-specific oligonucleotide probe based typing for the analysis of the MICA gene. We used a set of 30 oligonucleotide probes to screen for the polymorphisms in exons 2, 3, and 4, which account for the 16 known alleles. We report here the typing results of MICA for 103 B-cell lines that have been well characterized for HLA and describe the linkage disequilibrium between MICA and HLA-B. Unequivocal MICA typing was achieved for 85 of the 103 cells tested, 6 cells gave ambiguous MICA types, and a further 12 cells showed patterns consistent with them expressing at least one new MICA allele.
