title: CYP1A1 protein activity is associated with allelic variation in pterygium tissues and cells.
abstract: BACKGROUND
  A thymine/cytosine point mutation in the MSP I restriction site of cytochrome P450 1A1 (CYP1A1) has been linked to susceptibility to smoking-related cancers and is reported to result in increased enzyme activity. Therefore, we sought to determine whether allelic variation of CYP1A1 is associated with protein expression and protein activity in pterygium.
  
  
  METHODS
  We collected 150 pterygium samples and 50 normal conjunctiva samples, which served as controls. DNA samples were extracted from blood cells and then subjected to real-time ploymerase chain reaction (PCR) to determine CYP1A1 genotype. CYP1A1 protein expression was determined by immunohistochemical staining with a monoclonal antibody for CYP1A1. Pterygium epithelial cells (PECs), cultured in a serum-free culture medium, real-time PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to understand the effect of CYP1A1 allelic variation in protein expression and activity.
  
  
  RESULTS
  Forty-eight (33.3%) pterygium specimens tested positive for CYP1A1 protein expression. CYP1A1 protein expression was significantly greater in the pterygium group than in the control group (p<0.0001). In addition, CYP1A1 protein expression was associated with allelic variation. CYP1A1 protein expression was significantly greater in the m2/m2 group than in the m1/m1and m1/m2 groups (p=0.006). In the cell model, CYP1A1 protein expression and b[a]P 7,8-diol 9,10-epoxide (BPDE)-like DNA adducts increased in CYP1A1 m2/m2 (genotype T/T) PEC cells as compared with m1/m2 (genotype C/T) and m1/m1 (genotype C/C) cells.
  
  
  CONCLUSIONS
  CYP1A1 expression in pterygium correlates with allelic variation and can be used as an independent risk marker.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Peng
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Tsai
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chiang
authors.forename: Ying-Che
authors.initials: YC
authors.lastname: Huang
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D011625:Pterygium / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013624:Taiwan
chemical_list: C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1