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Estrogen receptor alpha gene (ESR1) polymorphism and its interaction with smoking and drinking contribute to susceptibility of systemic lupus erythematosus.
Immunologic Research 2017 August
The aim of this study is to investigate the association of estrogen receptor alpha gene (ESR1) polymorphisms, additional gene-gene, and gene-environment interaction with systemic lupus erythematosus (SLE) risk. SNPStats (available online at https://bioinfo.iconcologia.net/SNPstats ) was used to investigate the Hardy-Weinberg equilibrium (HWE) in controls and association between SNP and SLE risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the interactions among SNPs and environmental risk factors; SLE risk was significantly higher in carriers of rs2234693 C allele than those with TT (TC + CC versus TT), adjusted OR (95%CI) = 1.57 (1.21-2.06), and was also higher in carriers of rs9340799 G allele than those with AA (AG + GG versus AA), adjusted OR (95%CI) = 1.68 (1.24-2.13). However, we also find no association between rs2228480 and SLE risk after covariates adjustment. We found a significant two-locus model (p = 0.0010) involving rs2234693 and smoking; the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.70%. Smokers with TC or CC of rs2234693 genotype have the highest SLE risk, compared to never-smokers with TT of rs2234693 genotype, OR (95%CI) was 2.50 (1.65-3.42), after covariates adjustment for gender, age, alcohol drinking, and BMI. We found that C allele of rs2234693 and G allele of rs9340799 within ESR1 gene, their interaction between rs2234693 and current smoking were all associated with increased SLE risk.
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