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

Hori, Masaharu; Oniki, Kentaro; Nakagawa, Takehiro; Takata, Keiji; Mihara, Shuichi; Marubayashi, Toru; Nakagawa, Kazuko

doi:10.1111/j.1478-3231.2008.01794.x

Cited by 28 publications

(16 citation statements)

References 29 publications

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“…Also, the combined effect of the GSTP1 and GSTM1 variant genotypes on the risk of AD tended to be higher than the effect of GSTP1 or GSTM1 variants alone. Similar to our findings, several studies have indicated that the influences of GST genotypes on disease risk become more significant with an increase in the number of GST variant alleles (29)(30)(31). This is likely due to GST enzymes having similar substrate specificities.…”

Section: Discussionsupporting

confidence: 79%

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Chung

Shin

2009

Clinical Chemistry and Laboratory Medicine

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Background: Glutathione S-transferase (GST) enzymes are critical for detoxifying reactive oxygen species (ROS) and their products which have been implicated in the pathology of inflammatory diseases such as atopic dermatitis (AD). Methods:We investigated the effects of genetic polymorphisms of GST on the risk of AD in preschool age children. Biomarkers for oxidative stress were also evaluated with respect to GST genotype. Results: The GSTP1 Val105 allele was significantly associated with an increased risk of AD wodds ratio (OR)s1.62, p-0.05x. The combination of the GSTP1 Val105 allele and the GSTT1 null genotype further increased this risk by 2.3-fold (p-0.01). No association was observed for the GSTM1 null or GSTT1 null genotype alone. In children with AD, blood total antioxidant capacity was significantly less (p-0.001), while malondialdehyde was higher (ps0.12). Children with the GSTP1 Val105 allele had significantly lower concentrations of erythrocyte glutathione compared to GSTP1 Ile/Ile homozygotes (ps0.03). Conclusions: Our study suggests that the GSTP1 Val105 allele is an important determinant of susceptibility to AD in preschool age children and increased oxidative stress may play a role in the pathogenesis of AD.

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Section: Discussionsupporting

confidence: 79%

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Chung

Shin

2009

Clinical Chemistry and Laboratory Medicine

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“…Any disharmony in the pathways involved in triacylglycerol release, synthesis or oxidation could contribute to its accumulation in the liver (46). NAFLD is the most common reason for abnormal liver function, and may occur in 10-30% of the population (47). Amassment of triglycerides inside hepatocytes, chronic oxidative stress levels, insulin resistance, inflammation and fibrosis in combination make NAFLD a complicated disease (48).…”

Section: Discussionmentioning

confidence: 99%

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

et al. 2013

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BackgroundGenetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway.ObjectivesThe present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD.Patients and MethodsEighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms.ResultsA significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697).Conclusionsadiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations.

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“…Furthermore, GSTs have a lower expression in Caucasians compared to African–Americans, who have a lower prevalence of NAFLD (Stepanova et al, 2010). The GSTM1 -null genotype, shown to confer a higher risk of T2D, is also present at a higher frequency in NAFLD subjects compared to control (Hori et al, 2007, 2009). Thus, decreased activity of GSTs play a plausible role in NAFLD progression as a result of increased damage by oxidative stress (Table 3).…”

Section: Nafld and Drug Dispositionmentioning

confidence: 99%

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Belič¹,

Zanger²,

Rozman³

2013

Front. Gene.

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Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.

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

Cited by 28 publications

References 29 publications

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

Molecular Interactions between NAFLD and Xenobiotic Metabolism

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