Association between combinations of glutathione-S-transferase M1, T1 and P1 genotypes and non-alcoholic fatty liver disease
Association between combinations of glutathione-S-transferase M1, T1 and P1 genotypes and non-alcoholic fatty liver disease
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DOI：
10.1111/j.1478-3231.2008.01794.x
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发表时间：
2009-02-01
影响因子：
6.7
通讯作者：
Nakagawa, Kazuko
中科院分区：
文献类型：
--
作者：
Hori, Masaharu;Oniki, Kentaro;Nakagawa, Kazuko
谷胱甘肽-S-转移酶（GST）在抗氧化防御机制中起着至关重要的作用，通过解毒外源性物质和灭活氧化应激的内源性副产物。功能衰竭，作为GST基因型改变的后果，可能因此加重非酒精性脂肪肝（NAFLD）。本研究旨在探讨GST基因型是否会影响NAFLD的风险，并对253名日本健康筛查参与者进行横断面病例对照分析。GSTM 1 null、GSTT 1 null和GSTP 1 Ile 105 Val变异基因型为NAFLD的高危基因型，NAFLD的发病率为27.3%。NAFLD组GSTM 1无效基因型频率高于对照组[校正比值比（OR），2.00; 95%可信区间（CI），1.01-3.95]。此外，两种假定的高风险基因型的任何组合显示出更高的NAFLD风险，调整的OR为3.52（95%CI，1.08-11.43）-4.01（95%CI，1.28-12.56）。然而，GSTM 1 null和GSTT 1 null基因型组合的显著性仅在Bonferroni校正后保持。此外，NAFLD的危险性随着GST基因型的增多而增加，三种GST基因型携带者的OR值为9.67（95%CI：1.61-58.26），这是首次报道GST基因型对NAFLD发生的影响。这一发现应该在更大人群的进一步研究中得到证实，这可能有助于在早期阶段为NAFLD风险增加的受试者制定更有针对性的预防计划。
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.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.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).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.