The Role of Gene–Environment Interaction in the Etiology of SLE

Cigarette smoking may be associated with an increased risk of systemic lupus erythematosus (SLE). SLE results from a complex interaction between environmental and genetic risk factors. To evaluate modifying effect of the genetic polymorphisms involved in the metabolism of tobacco smoke on the association of cigarette smoking with SLE risk could be important for understanding of the pathogenesis of SLE. We investigated the relationship of four genetic polymorphisms (cytochrome P450 (CYP) 1A1 rs4646903, glutathione S-transferase (GST) M1 deletion and N-acetyltransferase 2 (NAT2)) to SLE risk with attention to interaction with cigarette smoking. CYP1A1 rs4646903 and NAT2 polymorphisms were significantly associated with SLE risk. The multiplicative interaction between any one of the three genetic polymorphisms and smoking were far from significant. There were significant additive interactions between smoking and either rs4646903 or NAT2. Specifically, the attributable proportion due to the interaction was estimated to be approximately 0.50. Future studies involving larger control and case populations, precisely and uniformly defined clinical classification of SLE and better smoking exposure histories will undoubtedly lead to a more thorough understanding of the role of various genes in SLE development.