Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

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).

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.

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).

Conclusion

Polymorphisms in XRCC1 Arg399Gln and APE1 Asp148Glu significantly increased the rate of apoptosis and risk of ulcerative colitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lawrance LC, Fiocchi C, Chakravarti S. Ulcerative colitis and Crohn’s disease: distinctive gene expression profiles and novel susceptibility candidate genes. Human Mol Genet. 2001;10:445–56.

    Article  CAS  Google Scholar 

  2. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 1996;313:17–29.

    PubMed  CAS  Google Scholar 

  3. Ozsavc D. Oxidative DNA damage and repair system. Adv Mol Med. 2007;3:57–61.

    Google Scholar 

  4. Kelsey KT, Park S, Nelson HH, Karagas MR. A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer. Cancer Epidemiol Biomar Prev. 2004;13:1337–41.

    CAS  Google Scholar 

  5. McCarty KM, Smith TJ, Zhou W, Gonzalez E, Quamruzzaman Q, Rahman M, et al. Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions. Carcinogenesis. 2007;28(8):1697–702.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang X, Miao X, Liang G, Hao B, Wang Y, Tan W, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res. 2005;65:722–6.

    PubMed  CAS  Google Scholar 

  7. Hung JR, Hall J, Brennan P, Boffetta P. Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Am J Epidemiol. 2005;162:925–42.

    Article  PubMed  Google Scholar 

  8. Yeh CC, Sung FC, Tang R, Chieh CR, Hsieh LL. Polymorphisms of the Xrcc1, Xrcc3, & Xpd genes, and colorectal cancer risk: a case-control study in Taiwan. BMC Cancer. 2005;5:1–8.

    Article  Google Scholar 

  9. Wang S, Gong Z, Chen R, Liu Y, Li A, Li G, et al. JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative stress-induced DNA single-strand breaks. Nucleic Acids Res. 2009;37:1936–50.

    Article  PubMed  CAS  Google Scholar 

  10. Marsin S, Vidal AE, Sossou M, Murcia JM, Page L, Boiteux S, et al. Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1. J Biol Chem. 2003;278:44068–74.

    Article  PubMed  CAS  Google Scholar 

  11. Rybicki AB, Conti VD, Moreira A, Cicek M, Casey G, Witte SJ. DNA repair gene XRCC1 and XPD polymorphisms and risk of prostate cancer. Cancer Epidemiol Biomark Prev. 2004;13:23–9.

    Article  CAS  Google Scholar 

  12. Krupa R, Blasiak J. An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. J Exp Clin Cancer Res. 2004;23:285–94.

    PubMed  CAS  Google Scholar 

  13. Li C, Liu Z, Wang LE, Strom SS, Lee JE, Gershenwald JE, et al. Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma. Carcinogenesis. 2006;27:1894–901.

    Article  PubMed  CAS  Google Scholar 

  14. Mort R, Mo L, McEwan C, Melton DW. Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer. Br J Cancer. 2003;89:333–7.

    Article  PubMed  CAS  Google Scholar 

  15. Jelonek K, Osok A, Pietrowska M, Borkowska M, Korfanty J, Rzeszowska J. Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. J Appl Genet. 2010;51:343–52.

    Article  PubMed  CAS  Google Scholar 

  16. Ito H, Matsuo K, Hamajima N, Mitsudomi T, Sugiura T, Saito T, et al. Gene environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis. 2004;25:1395–401.

    Article  PubMed  CAS  Google Scholar 

  17. Chiu HY, Tsao LV, Yang RC. Heat-shock response protects peripheral blood mononuclear cells (PBMCs) from hydrogen peroxide-induced mitochondrial disturbance. Cell Stress Chaperones. 2009;14:207–17.

    Article  PubMed  CAS  Google Scholar 

  18. Berndt IS, Huang YW, Fallin MD, Helzlsouer JK, Platz AE, Weissfeld LJ, et al. Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma. Cancer Res. 2007;67:1395–404.

    Article  PubMed  CAS  Google Scholar 

  19. Kasahara M, Osawa K, Yoshida K, Miyaishi A, Osawa Y, Inoue N, et al. Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. J Exp Clin Cancer Res. 2008;27:1–8.

    Article  Google Scholar 

  20. Stern MC, Siegmund KD, Corral R, Haike RW. XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. Cancer Epidemiol Biomark Prev. 2005;14:609–15.

    Article  CAS  Google Scholar 

  21. Shen M, Berndt SI, Rothman N, Mumford JL, He X, Yeager B, et al. Polymorphisms in the DNA base excision repair genes APE1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res. 2005;25:537–42.

    PubMed  CAS  Google Scholar 

  22. Nelson HH, Kelsey KT, Mott LA, Karagas MR. The XRCC1 Arg399Gln polymorphism, sunburn and non-melanoma skin cancer: evidence of gene–environment interaction. Cancer Res. 2002;62:152–5.

    PubMed  CAS  Google Scholar 

  23. Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010. doi:10.1155/2010/214074.

Download references

Acknowledgments

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

None.

Author information

Authors and Affiliations

  1. Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, India

    Avinash Bardia, Santosh K. Tiwari, Sivaram Gunisetty, Farha Anjum, Md. Aejaz Habeeb & Aleem A. Khan

  2. Department of Genetics, Osmania University, Hyderabad, 500 007, Andhra Pradesh, India

    Pratibha Nallari

Authors
  1. Avinash Bardia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Santosh K. Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sivaram Gunisetty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Farha Anjum
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pratibha Nallari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Md. Aejaz Habeeb
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aleem A. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aleem A. Khan.

Additional information

Responsible Editor: Andras Falus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bardia, A., Tiwari, S.K., Gunisetty, S. et al. Functional polymorphisms in XRCC-1 and APE-1 contribute to increased apoptosis and risk of ulcerative colitis. Inflamm. Res. 61, 359–365 (2012). https://doi.org/10.1007/s00011-011-0418-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-011-0418-2

Keywords

Search

Navigation