title: Interleukin-10 gene promoter and NFKB1 promoter insertion/deletion polymorphisms in systemic sclerosis.
abstract: Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrotic, immunological and vascular abnormalities. Nuclear factor-kB (NFKB), as a key transcription factor involved in the regulation of immune responses, appears to be a good candidate for studies on the pathogenesis of autoimmune diseases, as well as the interleukin-10 (IL-10) polymorphism, which other studies have suggested an association with SSc. Our objective was to study the association of NFKB and IL-10 gene polymorphisms with SSc. One hundred and fifty-one SSc patients and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-10 genes was made by polymerase chain reaction with sequence-specific primers (PCR-SSP), and NFKB gene typing was made by restriction fragment length polymorphism (RFLP). Patients underwent clinical evaluation, serology, Doppler echocardiography and chest high-resolution computed tomography. The frequency of IL-10 (-1082) GG genotype was found to be significantly higher in SSc patients (36.4%) as compared to healthy controls (22.4%) (P = 0.012). The frequency of heterozygous genotype GA was significantly lower (P = 0.004) in patients (38.4%) in comparison with control subjects (55.8%). A predominance of the high-producing IL-10 phenotype (GCC(+) /GCC(+) ) was observed in SSc patients compared with healthy controls (37.7% versus 24.5%, respectively; OR: 1.87, 95% CI: 1.10-3.19, P = 0.019). No significant difference was found in the allelic and genotype distribution of the NFKB promoter polymorphism between patients and controls. No statistically significant associations were found between IL-10 or NFKB polymorphisms clinical and laboratory features of SSc. Our results confirmed the association of the high-producing phenotype (GCC(+) /GCC(+) ) with increased risk for SSc, but found no correlation with NFKB polymorphisms.
authors.affiliation: Pós-Graduação em Medicina, Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: P H
authors.initials: PH
authors.lastname: Salim
authors.forename: M
authors.initials: M
authors.lastname: Jobim
authors.forename: M
authors.initials: M
authors.lastname: Bredemeier
authors.forename: J A B
authors.initials: JA
authors.lastname: Chies
authors.forename: J C T
authors.initials: JC
authors.lastname: Brenol
authors.forename: L F
authors.initials: LF
authors.lastname: Jobim
authors.forename: R M
authors.initials: RM
authors.lastname: Xavier
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000235:genetics*
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D016753:Interleukin-10