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Association between combinations of glutathione-S-transferase M1, T1 and P1 genotypes and non-alcoholic fatty liver disease


Kazuko Nakagawa MD, PhD, Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Kumamoto 862-0973, Japan
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Background/Aims: Glutathione-S-transferases (GSTs) play a crucial role in antioxidant defence mechanisms, by detoxifying xenobiotics and by inactivating endogenous byproducts of oxidative stress. Functional failure, as a sequel of an altered GST genotype, may thus aggravate non-alcoholic fatty liver disease (NAFLD). This study investigated whether the GSTs genotypes could affect the risk for NAFLD.

Methods: A cross-sectional case–control analysis included 253 Japanese participants in a health screening programme. The GSTM1 null, GSTT1 null and GSTP1 Ile105Val variant genotypes were determined as putative high-risk genotypes.

Results: The incidence of NAFLD was 27.3%. The frequency of the GSTM1 null genotype was higher in NAFLD than in the control [adjusted odds ratio (OR), 2.00; 95% confidence intervals (CI), 1.01–3.95]. Moreover, any combination of two putative high-risk genotypes exhibited a higher risk for NAFLD with an adjusted OR from 3.52 (95% CI, 1.08–11.43)–4.01 (95% CI, 1.28–12.56). However, the significance for the combination of GSTM1 null and GSTT1 null genotypes only remained after Bonferroni's correction. In addition, the risk for NAFLD increased as the number of high-risk genotypes, and the OR among three high-risk genotypes carriers was 9.67 (95% CI: 1.61–58.26).

Conclusion: This is the first report to show the impact of the GSTs genotypes on the development of NAFLD. This finding, which should be confirmed in further studies in larger populations, may help to develop a more targeted prevention programme at an early stage for subjects with an increased risk for NAFLD.

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