Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) patients exhibit alterations in cytokine production that may be relevant to SLE pathogenesis. There is evidence that cytokine gene polymorphisms control cytokine production; thus, these polymorphisms may be associated with SLE or its clinical manifestations. To establish the association of tumor necrosis factor alpha (TNF-alpha), transforming growth factor (TGF) beta1, interleukin (IL)-10, and IL-6 gene polymorphisms in Colombian SLE patients and their clinical manifestations, 120 SLE patients and 102 healthy controls were studied. Single nucleotide polymorphisms were studied by sequence-specific primers polymerase chain reaction (SSP-PCR) at: TNFalpha-308 (G/A), TGFbeta1 codon 10 (C/T) and codon 25 (G/C), IL-10 -1082 (G/A), -819 (C/T) and -592 (C/A), and IL-6 + 174 (G/C). Human leukocyte antigen (HLA)-DRbeta1 was typed by SSP-PCR. SLE patients had increased frequency of allele C at TGFbeta1 codon 25 (P = 0.0001, odds ratio (OR): 4.25, 95% confidence interval (CI): 2.17-8.35) and allele A at TNFalpha-308 (P = 0.0004 OR: 3.9, 95% CI: 1.65-5.80) compared with healthy controls. There was higher frequency of GC genotype at TGFbeta1 codon 25 in SLE patients (P < 0.0001). Extended genotypic analysis showed that SLE patients have decreased frequency of TNFalphaLow/TGFbeta1High (0.50) compared with healthy controls (0.80) (P < 0.0001). No association was found between these polymorphisms and SLE clinical manifestations except for Sm and Ro autoantibodies that were associated with TNFalpha allele A. There is an association between TNFalpha-308A/TGFbeta1 codon 25C with SLE susceptibility in Colombian population. This association may result in a highly inflammatory response with a decrease regulatory function mediated by TNFalpha and TGFbeta1, respectively. The TNFalpha-308A/TGFbeta1 25C genotype may be one component of genetic susceptibility to SLE in Colombian population.

Interleukin-6 promoter polymorphisms (-174 G/C) in Malaysian patients with systemic lupus erythematosus

“…This observation again suggests the role of the complex interaction of multiple genes and the involvement of other factors in the development of SLE. Overall, our results do not agree with several other studies carried out on other world populations (10,15,16) and these contradictory results could be due to the genetic heterogeneity of SLE in different ethnicities.…”

“…The translation of IL-6 RNA and post-translational processing result in the formation of a 21-to 28-kDa protein with 128 amino acids (14). In the present study, we investigated whether there is an association between SLE susceptibility and single nucleotide polymorphisms located in the promoter region of the IL-6 gene (-174 G/C) in our Malaysian SLE patients, although many negative correlation results have been observed in various studies in the world (10,15,16).…”

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

“…The resulting defects in immune tolerance eventually lead to an abnormal response to self-antigens and the tissue damage seen in diseases such as asthma, systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis [4,5,8,9,[16][17][18][19][20]. Bearing in mind the role of defects in selfantigen recognition by T-lymphocytes in autoimmune processes, polymorphisms in the IL-4 gene may lead to a magnification of IL-4 signaling and thus the Th-2 immune response.…”

“…One would intuitively choose genes whose products are more likely to be important in the regulation of cellular or humoral immune responses. We focused in this study on IL-4, IL-10 and TGF-b gene polymorphisms, considering that polymorphisms in these three genes have been associated with immune conditions such as atopy, systemic lupus erythematosus and rheumatoid arthritis [4][5][6][7][8][9]. We hypothesized O that these anti-inflammatory mediators might be involved in GD pathogenesis.…”

Meta-analysis of TNF-α promoter –308A/G polymorphism and SLE susceptibility in Asian populations

“…Remaining 28 studies were retrieved for more detailed evaluation [11][12][13][14]. Of these, 18 were not conducted in Asian populations and were excluded [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Thus, 10 studies were selected in PubMed (Table 1) [11][12][13][14][17][18][19][20][21][22].…”