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 regulatory single nucleotide polymorphism located in the 5' region (-169T/C) of the Fc receptor-like 3 (FCRL3_3) gene has been associated with both susceptibility and protection in immune diseases. This case-control study aimed to evaluate the association between FCRL3 polymorphisms and juvenile rheumatoid arthritis (JRA), asthma, and childhood-onset systemic lupus erythematosus (SLE) in a Mexican population. We performed PCR-based genotyping to identify four FCRL3 single nucleotide polymorphisms (FCRL3_3 to FCRL3_6) in patients with JRA (n=202), asthma (n=239), or childhood-onset SLE (n=377), and healthy controls (n=400). The case-control analysis showed a male-gender dependent association between the FCRL3_3C, FCRL3_5C, and FCRL3_6A alleles and either JRA (OR=0.57, p=0.003; OR=0.55, p=0.002; OR=0.53, p=0.0007, respectively) or asthma (OR=0.72, p=0.04; OR=0.74, p=0.05; OR=0.70, p=0.02, respectively). As expected, minor alleles of these SNPs with the CGCA haplotype were also significantly associated with JRA (OR=0.35, p=0.00005) and asthma (OR=0.61, p=0.007). We found no association between FCRL3 SNPs or haplotypes and childhood-onset SLE. These results supported the notion that FCRL3 is involved in the etiology of several immune diseases. Our results also suggested that SNPs located in the FCRL3 gene were protective against JRA and asthma in male Mexican patients.
Subject(s)
Arthritis, Juvenile/genetics , Asthma/genetics , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , Receptors, Immunologic/genetics , Adolescent , Adult , Alleles , Arthritis, Juvenile/epidemiology , Asthma/epidemiology , Case-Control Studies , Female , Gene Frequency , Genotyping Techniques , Haplotypes , Humans , Linkage Disequilibrium , Lupus Erythematosus, Systemic/epidemiology , Male , Mexico/epidemiology , Sex FactorsABSTRACT
RB1 mutation detection has greatly improved the clinical management of retinoblastoma and provides critical information to predict the risk of inheriting the disease. We screened for RB1 gene sequence alterations in both peripheral blood and tumor specimens from a total of 48 Mexican retinoblastoma patients using an SSCP-based screening approach followed by sequencing. Overall, 21 (43.8%) cases were bilateral and 27 (56.2%) were unilateral. Interestingly, 51.8% of unilateral patients developed the tumor before age 1 year and 10 of which (71.4%) were diagnosed before the age of 6 months. Thirteen different oncogenic mutations were detected in 14/48 (29.2%) patients, 9 of which were germline (64.3%). Six of these mutations are novel (IVS3-1G>T, 125X, 389X, 610X, 750X and -149G>T). The most frequent types of mutation were frameshift and nonsense (30.8% each). Moreover, 5 intronic variants were identified, two of which are novel (g.41908 C/A and g.161976del6T). Loss of heterozygosity of the RB1 gene as assessed by intron1/BamHI and intron17/XbaI intragenic markers was 50.0% (18 of 36 informative cases), being higher in tumors with known mutations (76.9% vs 34.8%). This low mutation detection rate and the earlier age at diagnosis in unilateral retinoblastoma cases suggest that other RB1 inactivating mechanisms could be present in the retinoblastoma development. In this study, mutation analysis was not helpful to distinguish sporadic and hereditary retinoblastoma, so, other approaches are needed to improve the molecular diagnosis of retinoblastoma and supports further investigations of Mexican retinoblastoma patients.
Subject(s)
Genes, Retinoblastoma , Retinal Neoplasms/genetics , Retinoblastoma Protein/genetics , Retinoblastoma/genetics , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis , Female , Functional Laterality , Humans , Infant , Loss of Heterozygosity , Male , Mexico , Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded ConformationalABSTRACT
This study was conducted to determine the frequency of the most common fusion genes in Mexican pediatric patients with acute lymphoblastic leukemia (ALL). Molecular analysis using RT-PCR was carried out in 53-blood samples: 52 patients with de novo ALL and one with relapsed ALL. The ETV6-RUNX1 fusion was found in 7 cases (13.5%), BCR-ABL fusion was detected in 2 cases (3.8%), and 6 patients (11.5%) expressed the chimeric gene E2A-PBX1. The prevalence of E2A-PBX1 is one of the highest that has been described thus far in childhood ALL. Furthermore, we detected both the BCR-ABL, and E2A-PBX1 fusion in the relapsed patient. With regards to the immunophenotype, ETV6-RUNX1 was expressed in both pre-B and T-cell cases, while the presence of E2A-PBX1 and BCR-ABL was associated with the pre-B ALL phenotype. The prevalence of E2A-PBX1 in Mexican pediatric cases supports the existence of ethnic differences in the frequency of molecular markers of ALL.
