title: Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population.
abstract: BACKGROUND
  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 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.
  
  
  CONCLUSIONS
  Our results suggest the involvement of CYP2E1 as a susceptibility gene for SLE in the Chinese population.
authors.affiliation: The Research Base of TCM Syndrom, Fujian University of Traditional Chinese Medicine, Huatuo Road No.1, Fuzhou 350108, PR China.
authors.forename: Ling-hong
authors.initials: LH
authors.lastname: Liao
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Man-Po
authors.initials: MP
authors.lastname: Lai
authors.forename: Shun-Le
authors.initials: SL
authors.lastname: Chen
authors.forename: Madeline
authors.initials: M
authors.lastname: Wu
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D019392:Cytochrome P-450 CYP2E1