Abstract
IntroductionCytochrome P-450 2E1 (CYP2E1) is an important member of the CYP superfamily, which is involved in the metabolism and activation of many low molecular weight toxic compounds. We tried to investigate the possible association of CYP2E1 tag single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese Han population.MethodsThe 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.ResultsTag 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.ConclusionsOur results suggest the involvement of CYP2E1 as a susceptibility gene for SLE in the Chinese population.
Highlights
Cytochrome P-450 2E1 (CYP2E1) is an important member of the cytochrome P-450 enzymes (CYPs) superfamily, which is involved in the metabolism and activation of many low molecular weight toxic compounds
The “A” allele was associated with slightly higher risk (OR = 1.165, 95% confidence intervals (CI) 1.073 to 1.265, P = 2.75E-4) and “A/A” genotype carriers were with even higher systemic lupus erythematosus (SLE) risk (OR = 1.464, 95% CI 1.259 to 1.702, P = 7.48E-7)
After conducting a two-stage study involving the genotyping and clinical evaluation of 876 SLE patients and 680 healthy controls recruited among Han Chinese, we provide the first time evidence for the statistically significant association for single nucleotide polymorphism (SNP) rs2480256, of CYP2E1 with SLE
Summary
Cytochrome P-450 2E1 (CYP2E1) is an important member of the CYP superfamily, which is involved in the metabolism and activation of many low molecular weight toxic compounds. We tried to investigate the possible association of CYP2E1 tag single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese Han 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. CYP2E1, an important member of CYP superfamily, is involved in the metabolism and activation of many low molecular weight toxic compounds, including ethanol, benzene, nitrosamine and TCE [15]. We undertook this study to evaluate any association between CYP2E1 genetic polymorphisms and SLE in a Chinese study population
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