title: Functional polymorphisms in XRCC-1 and APE-1 contribute to increased apoptosis and risk of ulcerative colitis.
abstract: OBJECTIVE
  The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms in apoptosis and the risk of ulcerative colitis (UC).
  
  
  METHODS
  Blood samples from 384 unrelated subject (age range 18-65 years; 171 with UC, 213 healthy controls) were collected after colonoscopy. Genomic DNA was isolated and genotyped for XRCC1                            Arg399Gln and APE1                            Asp148Glu using a confronting two-pair primers polymerase chain reaction. Apoptosis and intracellular reactive oxygen species (ROS) levels in peripheral blood mononuclear cells were measured using annexin-V and H(2)DCFDA assay, respectively.
  
  
  RESULTS
  The frequency of genotype Arg399Gln (heterozygous) of XRCC1 gene was significantly higher in patients with UC than the controls (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.13-2.64; p = 0.01). Similarly the genotypic frequency of APE1                            Asp148Glu showed statistically significant incidence among UC subjects (OR 1.54; 95% CI 1.02-2.33; p = 0.04). Polymorphism in XRCC1                            Arg399Gln and APE1                            Asp148Glu together considerably increased the risk of UC (OR 2.303; 95% CI 1.43-3.69; p = 0.0007). ROS levels were high in UC subjects compared with controls (p = 0.01).
  
  
  CONCLUSIONS
  Polymorphisms in XRCC1                            Arg399Gln and APE1                            Asp148Glu significantly increased the rate of apoptosis and risk of ulcerative colitis.
authors.affiliation: Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500 058, Andhra Pradesh, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bardia
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Tiwari
authors.forename: Sivaram
authors.initials: S
authors.lastname: Gunisetty
authors.forename: Farha
authors.initials: F
authors.lastname: Anjum
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nallari
authors.forename: Md Aejaz
authors.initials: MA
authors.lastname: Habeeb
authors.forename: Aleem A
authors.initials: AA
authors.lastname: Khan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase