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 (À1082) 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.

Molecular Genetic Mechanisms of Chronic Urticaria

“…Moreover, it has been shown to induce pro- and anti-inflammatory responses 55. The genetic variants -1082A/G, -819C/T, and 592A/C in the promoter region of the IL-10 gene have been described frequently in association with cutaneous diseases, while their influence on IL-10 production is unclear 58-61. A genetic association of -819T>C in IL-10 with AIU, including both AIAU and AICU, was identified in a Korean population 62.…”

Analysis of IL-6, IL-10 and NF-κB Gene Polymorphisms in Aggressive and Chronic Periodontitis

“…The mechanism behind NF-κB1 in relation to disease susceptibility remains unclear although -94 del ATTG has been proven to reduce activation of NF-κB1 transcription. A meta-analysis suggests an association between NF-κB1 -94ins/delATTG promoter polymorphism to certain autoimmune and inflammatory disease (diabetes mellitus, ulcerative colitis and psoriasis) in Asian population but not in the Caucasian population (6,27). However, only one study suggested significant association of the homozygous mutation genotype del/del with the occurrence of aggressive periodontitis in a cohort of German Caucasians (7).…”

“…Five members of the NF-κB family have been identified, and they are NF-κB1 (p105/p50), NF-κB2 (p100/p52), RelA (p65), RelB and c-Rel. Several polymorphisms have been identified in the promoter region of NF-κB1 gene, which is insertion/deletion (-94ins/delATTG) (6). However, one study conducted on periodontal disease reported that del/del genotype of NF-κB1 gene was associated with aggressive periodontitis (7).…”

Investigation of NF-κB1 and NF-κBIA Gene Polymorphism in Non-Small Cell Lung Cancer

“…Recently, many studies with animal models and cell culture systems indicate the interplay between NF- κ B and lung carcinogenesis, which emphasizes the importance of targeting the NF- κ B signaling pathway for lung cancer treatment and chemoprevention [7]. NF- κ B, a nuclear transcription factor [8], was first identified in 1986 by Sen and Baltimore [9]. It was initially observed to be a transcription factor binding to the intronic enhancer of the kappa light chain gene (the κ B site) in B cells, but it was later shown to be present in every cell type [10].…”