In view of documented evidence that catechol estrogen-DNA adducts serve as 
epitopes for binding of anti-nuclear antibodies, genetic polymorphisms of the 
xenobiotic metabolic pathway involved in estrogen metabolism might contribute 
towards pathophysiology of systemic lupus erythematosus (SLE). To test this 
hypothesis, a case-control study was conducted. Cytochrome P 450 1A1 (CYP1A1) m4 
(OR: 4.93, 95% CI: 1.31-18.49), catecholamine-o-methyl transferase (COMT) H108L 
(OR: 1.39, 95% CI: 1.03-1.88) and glutathione-S-transferase (GST) T1 null (OR: 
1.83, 95% CI: 1.11- 3.01) variants showed association with SLE risk. SHEsis 
web-based platform analysis showed mild to moderate linkage disequilibrium 
between the CYP1A1 ml, m2 and m4 variants (D': 0.19-0.37). Among the different 
haplotypes of CYP1A1, CAC-haplotype harboring CYP1A1 ml variant showed 
association with SLE risk (OR: 1.46, 95% CI: 1.11-1.92). Multifactor 
dimensionality reduction analysis (MDR) showed potential gene-gene interactions 
between the phase II variants i.e. COMT H108L x GSTT1 null x GSTM1 null (p < 
0.0001) and also between the phase II and I variants i.e. COMT H108L x GSTTI 
null x CYP1A1 ml x CYP1A1 m2 in inflating the risk of SLE by 3.33-folds (95% CI: 
2.30-4.82) and 4.00-folds (95% CI: 2.77-5.78), respectively. To conclude, 
hyperinducibility of CYP1A1 due to ml and m4 variants and defective phase-II 
detoxification due to COMT H108L and GSTT1 null variants increase the 
susceptibility to SLE.