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Interleukin‐10 Gene Promoter and NFKB 1 Promoter Insertion/Deletion Polymorphisms in Systemic Sclerosis
Author(s) -
Salim P. H.,
Jobim M.,
Bredemeier M.,
Chies J. A. B.,
Brenol J. C. T.,
Jobim L. F.,
Xavier R. M.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12020
Subject(s) - genotype , restriction fragment length polymorphism , pathogenesis , allele , immunology , promoter , polymerase chain reaction , medicine , gene polymorphism , typing , gene , biology , gastroenterology , genetics , gene expression
Systemic sclerosis ( SS c) 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 SS c. Our objective was to study the association of NFKB and IL ‐10 gene polymorphisms with SS c. One hundred and fifty‐one SS c 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, D oppler echocardiography and chest high‐resolution computed tomography. The frequency of IL ‐10 (−1082) GG genotype was found to be significantly higher in SS c 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 SS c 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 SS c. Our results confirmed the association of the high‐producing phenotype ( GCC + / GCC + ) with increased risk for SS c, but found no correlation with NFKB polymorphisms.