Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus

This study aims to explore the impact of interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and its interaction with environment on the risk of systemic lupus erythematosus (SLE). Chi-square testing method was used to investigate whether the distributions for genotype of four SNPs were differed from Hardy-Weinberg equilibrium (HWE). Logistic regression was used to test the association between IL-10 SNPs and SLE risk. The best interaction combinations between IL-10 SNPs and environmental factors were assessed by generalized multifactor dimensionality reduction (GMDR). Both rs1800896-G and rs1800871-T alleles were associated with increased risk of SLE, the odds ratios (ORs) (95% confidence interval (CI)) for the two SNPs were 1.68 (1.25–2.09) and 1.47 (1.12–1.94), respectively. Then, we used the GMDR method to analyze the high-order interactions of four SNPs within IL-10 gene and environmental factors on SLE risk. We found a significant interaction combination (two-locus model with P = 0.001) between rs1800896 and smoking, after adjusting for gender, age, body mass index (BMI), and alcohol drinking. We also used two-variable stratified analysis by logistic regression to analyze the synergistic effect between two variables (rs1800896 and smoking), which had significant significance in GMDR model. We found that current smokers with rs1800896-AG or GG genotype have the highest SLE risk, compared with never smokers with the rs1800896-AA genotype, OR (95% CI) = 2.24 (1.52–3.58). The rs1800896-G and rs1800871-T alleles and interaction between rs1800896 and current smoking were all associated with increased risk of SLE.