• Vol. 36 No. 2, 91–95
  • 15 February 2007

Interleukin-18 Promoter Gene Polymorphisms in Chinese Patients With Systemic Lupus Erythematosus: Association With CC Genotype at Position –607

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ABSTRACT

Introduction: Interleukin-18 (IL-18) is a Th1 cytokine, which is postulated to play a role in systemic lupus erythematosus (SLE). Two single nucleotide polymorphisms (SNPs) in the IL-18 promoter gene region were found to influence the quantitative expression of the IL-18 protein. The aim of this study was to determine whether IL-18 promoter gene polymorphisms are associated with SLE. Materials and Methods: One hundred and thirteen Chinese SLE patients and 218 Chinese healthy individuals were recruited. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR and restriction fragment length polymorphism (RFLP) analysis were used to genotype the DNA samples for SNP-137 and SNP607. The following genotypes were obtained: SNP(-607) AA, AC, CC and SNP(-137) GG, GC, CC. Plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay. Results: the frequency of SNP-607/CC genotype was significantly higher in SLE patients (Pc < 0.05) while genotype SNP-607/AC was significantly decreased in SLE patients compared to the control group (Pc <0.05). Plasma IL-18 concentrations were significantly higher in SLE patients than in control subjects (P <0.05). Both patients and control subjects with CC and AC genotypes have significantly higher IL-18 concentrations than those with AA genotype. Conclusion: The IL-18 promoter gene polymorphism SNP–607 C allele is associated with SLE and may result in the enhanced production of IL-18 protein in SLE and normal individuals.


Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of high titres of autoantibodies and associated with a diverse array of clinical manifestations that include arthritis, vasculitis and nephritis. It is a complex disease, and genetic and environmental factors contribute to the disease pathogenesis. Abnormal Th1 and Th2 cytokines profiles might be involved in the pathogenesis of SLE. Peripheral blood mononuclear cells of SLE patients show decreased production of the Th1 cytokines IL-2, IFN-γ, TNF-α and IL-12 and upregulation of the Th2 cytokines IL-4 and IL-10.1-3 Such cytokines profiles may account for the polyclonal B-cell activation observed in SLE. Other studies, on the contrary, have demonstrated that the serum levels of Th1 cytokines IL-12, TNF-α and IFN-γ are significantly higher in SLE patients.4-6

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