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

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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.

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Authors and Affiliations

  1. Academic Unit of Surgery, The General Infirmary, Great George Street, Leeds, LS1 3EA

    Sakhawat Hussain Rahman MBChB, MD, MRCS, Chaddha Nanny MBChB, Khadija Ibrahim & Michael J. McMAHON ChM, PhD, FRCS

  2. Post-graduate Medical School, Derriford Hospital, Plymouth, Derby City General Hospital, Derby, DE22 3NE, UK

    Derek O’reilly FRCS & Andrew J. Kingsnorth MD, FRCS

  3. Academic Unit of Surgery, Derby City General Hospital, Derby, DE22 3NE, UK

    Michael Larvin MBChB, MD, FRCS

  4. Division of Surgery, James’s University Hospital, Level 8, Clinical Sciences Building, St., Beckett Street, Leeds, LS9 7TF, UK

    Sakhawat Hussain Rahman MBChB, MD, MRCS

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  1. Sakhawat Hussain Rahman MBChB, MD, MRCS
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Correspondence to Sakhawat Hussain Rahman MBChB, MD, MRCS.

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Rahman, S.H., Nanny, C., Ibrahim, K. et al. Genetic Polymorphisms of GSTT1, GSTM1, GSTP1, MnSOD, and Catalase in Nonhereditary Chronic Pancreatitis: Evidence of Xenobiotic Stress and Impaired Antioxidant Capacity. Dig Dis Sci 50, 1376–1383 (2005). https://doi.org/10.1007/s10620-005-2790-7

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  • DOI: https://doi.org/10.1007/s10620-005-2790-7

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