single-nucleotide polymorphisms and haplotype of cyp2e1 gene associated with systemic lupus erythematosus in chinese populationcyp2e1基因的单核苷酸多态性和单体型与系统性红斑狼疮相关的中国人口.pdf

Liao et al. Arthritis Research Therapy 2011, 13:R11 /content/13/1/R11 RESEARCH ARTICLE Open Access Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population 1 2 2 3 2 3* Ling-hong Liao , Hao Zhang , Man-Po Lai , Shun-Le Chen , Madeline Wu , Nan Shen Abstract Introduction: 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. Methods: 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. Results: 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