Digestive Diseases and Sciences

, Volume 50, Issue 7, pp 1376–1383

Genetic Polymorphisms of GSTT1, GSTM1, GSTP1, MnSOD, and Catalase in Nonhereditary Chronic Pancreatitis: Evidence of Xenobiotic Stress and Impaired Antioxidant Capacity

  • Sakhawat Hussain Rahman
  • Chaddha Nanny
  • Khadija Ibrahim
  • Derek O’reilly
  • Michael Larvin
  • Andrew J. Kingsnorth
  • Michael J. McMAHON
Article

DOI: 10.1007/s10620-005-2790-7

Cite this article as:
Rahman, S.H., Nanny, C., Ibrahim, K. et al. Dig Dis Sci (2005) 50: 1376. doi:10.1007/s10620-005-2790-7

Abstract

Epidemiological studies have demonstrated a variety of potential environmental factors that may alter susceptibility to chronic pancreatitis (CP) through oxidative/xenobiotic stress; however, a direct causal and mechanistic role has not been established. We aimed (1) to determine the prevalence of functional genetic polymorphisms in the antioxidant enzymes, glutathione S-transferase GSTM-1, GSTP-1, and GSTT-1, manganese superoxide dismutase, and catalase in CP and (2) to reveal evidence of oxidative stress in patients with CP by measuring whole-blood glutathione redox status. In total, 122 patients with CP (75 alcohol-induced [AlCP], 33 idiopathic [ICP], and 13 hereditary) and 245 age- and sex-matched controls were recruited. The prevalence of the functional GSTT-1 genotype (GSTT-1*A) was significantly higher in CP (88.5%) compared to healthy controls (76%; χ2 = 7.26, P = 0.007). Stratification to disease etiology demonstrated that the GSTT-1*A genotype was also significantly more prevalent among patients with ICP (94%; P = 0.02; 95% CI, 0.04–9.16) but not in those with AlCP. In 22 patients with stable CP, the whole-blood glutathione concentration (median [IQR]: 72 μmol/L [21–181 μmol/L]) and the glutathione redox ratio (GSH/GSSG) (median [IQR]: 9 (3–77]) were significantly reduced compared to those in 20 healthy volunteers (median [IQR]: 815 μmol/L [679–1148 μmol/L], P < 0.001, and 96 [52–347], P = 0.005, respectively). We conclude that the GSTT-1 functional genotype is associated with ICP. Evidence of altered glutathione redox status suggests that this disease modification may be a consequence of oxidative stress or the bioactivation of xenobiotics.

Key Words

antioxidants genetic polymorphisms chronic pancreatitis GSTT-1 

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Sakhawat Hussain Rahman
    • 1
    • 4
  • Chaddha Nanny
    • 1
  • Khadija Ibrahim
    • 1
  • Derek O’reilly
    • 2
  • Michael Larvin
    • 3
  • Andrew J. Kingsnorth
    • 2
  • Michael J. McMAHON
    • 1
  1. 1.Academic Unit of SurgeryLeeds
  2. 2.Post-graduate Medical School, Derriford Hospital, PlymouthDerby City General HospitalDerbyUK
  3. 3.Academic Unit of SurgeryDerby City General HospitalDerbyUK
  4. 4.Division of SurgeryJames’s University HospitalLeedsUK

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