Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus

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) beta 1, 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: TNF alpha -308 (G/A), TGF beta 1 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)-DR beta 1 was typed by SSP-PCR. SLE patients had increased frequency of allele C at TGF beta 1 codon 25 (P = 0.0001, odds ratio (OR): 4.25, 95% confidence interval (CI): 2.17-8.35) and allele A at TNF alpha -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 TGF beta 1 codon 25 in SLE patients (P < 0.0001). Extended genotypic analysis showed that SLE patients have decreased frequency of TNF alpha Low/TGF beta 1High (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 TNF alpha allele A. There is an association between TNF alpha-308A/TGF beta 1 codon 25C with SLE susceptibility in Colombian population. This association may result in a highly inflammatory response with a decrease regulatory function mediated by TNF alpha and TGF beta 1, respectively. The TNF alpha -308A/TGF beta 1 25C genotype may be one component of genetic susceptibility to SLE in Colombian population.