Functional polymorphisms in XRCC- 1 and APE- 1 contribute to increased apoptosis and risk of ulcerative colitis.

Bardia, Avinash; Tiwari, Santosh; Gunisetty, Sivaram; Anjum, Farha; Nallari, Pratibha; Habeeb, Md.; Khan, Aleem

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). Materials and 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 Arg399 Gln and APE1 Asp148 Glu 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 HDCFDA assay, respectively. Results: The frequency of genotype Arg399 Gln (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 Asp148 Glu showed statistically significant incidence among UC subjects (OR 1.54; 95% CI 1.02-2.33; p = 0.04). Polymorphism in XRCC1 Arg399 Gln and APE1 Asp148 Glu 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). Conclusion: Polymorphisms in XRCC1 Arg399 Gln and APE1 Asp148 Glu significantly increased the rate of apoptosis and risk of ulcerative colitis.

APURINIC acid; ENDONUCLEASES; ULCERATIVE colitis; POLYMERASE chain reaction; POLYMERIZATION

Inflammation Research, 2012, Vol 61, Issue 4, p359

1023-3830

Academic Journal

10.1007/s00011-011-0418-2