title: Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric population.
abstract: There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.
authors.affiliation: Genomic of Complex Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Jiménez-Morales
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Julián
authors.initials: J
authors.lastname: Ramírez-Bello
authors.forename: Edmundo
authors.initials: E
authors.lastname: Bonilla-González
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.forename: Guillermo
authors.initials: G
authors.lastname: Escamilla-Guerrero
authors.forename: Francisco
authors.initials: F
authors.lastname: Cuevas
authors.forename: Francisco
authors.initials: F
authors.lastname: Espinosa-Rosales
authors.forename: Nora Ernestina
authors.initials: NE
authors.lastname: Martínez-Aguilar
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Vera
authors.forename: Vicente
authors.initials: V
authors.lastname: Baca
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008800:Mexico; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha