Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population

The coding and flanking regions of the CYP2E1 gene were scanned for polymorphisms and tag SNPs were selected. A two-stage case-control study was performed to genotype a total of 876 SLE patients and 680 geographically matched healthy controls (265 cases and 288 controls in stage I and 611 cases and 392 controls in stage II). SLE associations of alleles, genotypes and haplotypes were tested by age and sex adjusted logistic regression. The gene transcription quantitation was carried out for peripheral blood mononuclear cell (PBMC) samples from 120 healthy controls.Tag SNP rs2480256 was found significantly associated with SLE in both stages of the study. The "A" allele was associated with slightly higher risk (odds ratio (OR) = 1.165, 95% confidence interval (CI) 1.073 to 1.265, P = 2.75E-4) and "A/A" genotype carriers were with even higher SLE risk (OR = 1.464 95% CI 1.259 to 1.702, P = 7.48E-7). When combined with another tag SNP rs8192772, we identified haplotype "rs8192772-rs2480256/TA" over presented in SLE patients (OR 1.407, 95% CI 1.182 to 1.675, P = 0.0001) and haplotype "TG" over presented in the controls (OR 0.771, 95% CI 0.667 to 0.890, P = 0.0004). The gene transcription quantitation analysis further proved the dominant effect of rs2480256 as the "A/A" genotype showed highest transcription.Our results suggest the involvement of CYP2E1 as a susceptibility gene for SLE in the Chinese population.Systemic lupus erythematosus (SLE (OMIM 152700)) is a chronic autoimmune disease with heterogeneous clinical features ranging from mild forms to progressive end organ damage. It is characterized by humoral and cellular immunity to self antigens. Approximately 90% of SLE patients are female. Epidemiological studies suggest the contribution of multiple factors including genetics, environmental exposure and gene-environmental interactions in the etiology of SLE [1-4] The significant difference of SLE prevalence between African descents in industrialized countries and res