Functional polymorphisms in XRCC-1 and APE-1 contribute to increased apoptosis and risk of ulcerative colitis
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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 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 H2DCFDA assay, respectively.
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).
Polymorphisms in XRCC1 Arg399Gln and APE1 Asp148Glu significantly increased the rate of apoptosis and risk of ulcerative colitis.
KeywordsUlcerative colitis X-ray cross-complementing group 1 Apurinic/apyrimidinic endonuclease 1 Apoptosis Reactive oxygen species
We would like to thank Mrs. Deepika, Research Fellow, Department of Genetics, Osmania University for statistical analysis. The authors would also like to acknowledge Mr. Pinaki Ghosh and Mr. Arvind Ghule, Senior Research Fellows, Pune College of Pharmacy, Pune, for sharing ApoAlert™ Annexin V Apoptosis Kit for our experiments. The study was not supported by any intra- or extramural funds.
Conflict of interest
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