Association of IL-6 -174 G>C polymorphism with the risk of SLE among south Indians: evidence from case–control study and meta-analysis

Abstract

Cytokines play a direct role in disease pathogenesis of systemic lupus erythematosus (SLE). Elevated levels of serum IL-6 are well documented with the disease activity and anti-dsDNA antibodies in SLE. The 5′ promoter region of the IL-6 gene has been shown to play a significant role in the regulation of gene expression. In view of this, the current study aimed to investigate the possible association of 5′ promoter polymorphisms G-597A (rs1800797), G-572C (rs1800796) and G-174C (rs1800795) with the risk of SLE. Analysis of 468 subjects (202 SLE patients and 266 controls) showed a significant association of the -174 G/C variant with the SLE risk in both dominant and recessive model (odds ratio (OR) 3.20, 95% confidence interval (CI) 1.18–8.69, P = 0.020 and OR 2.02, 95% CI 1.35–3.02, P = 0.0005), respectively. The ‘G allele of the -174 loci (OR 1.97, 95% CI 1.39–2.78, P = 0.00012) has shown significant distribution between the cases and controls. The haplotype analysis revealed that AGG haplotype carriers are more frequent in cases than controls and found a significant positive association (OR 1.394, 95% CI 1.07–7.12, P = 0.028) with SLE. In addition, we also undertook a meta-analysis on 13 study groups for -174 G/C, comprising a total of 1585 cases and 1690 controls. The pooled OR also suggested a significant association of -174 G/C with SLE (OR 1.36, 95% CI 1.22–1.53, P < 0.05). In conclusion, the presence of the G allele at the IL-6 polymorphic promoter loci -174 is a risk factor and might influence SLE disease and pathogenesis. Meta-analysis has also suggested the overall correlation between -174 G/C polymorphism and SLE risk.