The Genetics of Nonalcoholic Fatty Liver Disease: Role of Diet as a Modifying Factor

Kalafati, Ioanna-Panagiota; Borsa, Dimitra; Dedoussis, George

doi:10.1007/s13668-014-0085-3

Cited by 6 publications

(4 citation statements)

References 140 publications

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“…26 Emergent research has shown nutritional regulation of PNPLA3 15 26 so that patients with NAFLD carrying the PNPLA3 risk allele might benefit more from weight loss but less from omega-3 supplementation. [26][27][28][29] Diet lifestyle modification is more effective in decreasing liver steatosis in PNPLA3 I148M carriers than in non-carriers. 29 30 Liver fat content is influenced by the interaction between PNPLA3 variants and high carbohydrate intake, specifically sugar.…”

Section: Open Accessmentioning

confidence: 99%

Nutrigenetics-based intervention approach for adults with non-alcoholic fatty liver disease (NAFLD): study protocol for a randomised controlled feasibility trial

et al. 2021

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IntroductionLifestyle interventions targeting weight loss and improved dietary patterns are the recommended treatment for non-alcoholic fatty liver disease (NAFLD). However, the effectiveness of current established diet therapies is suboptimal. The patatin‐like phospholipase domain containing 3 (PNPLA3) gene modifies disease outcome and hepatic lipid handling, but the role of PNPLA3 variants in modulating responsiveness to different diet therapies is unknown.Methods and analysisThis project aims to assess the feasibility of conducting a genotype-driven randomised controlled trial (RCT) investigating the differential response to a Mediterranean diet (MD) intervention of NAFLD patients according to genotype for the rs738409 (I148M) variant of PNPLA3. A single-centre randomised controlled feasibility trial will be undertaken. We will recruit 60 adults with NAFLD from a tertiary hepatology centre in England. In a cross-over design, participants will undertake Diet 1 (MD) and Diet 2 (control) for 4 weeks, in random order (1:1 allocation), separated by a 4 weeks washout period. Participants will complete one-to-one diet and lifestyle consultations at baseline, end of diet phase 1, end of washout and end of diet phase 2. Participants will be advised to maintain baseline levels of physical activity and body weight. The primary outcome is the acceptability and feasibility of the intervention protocol. Secondary outcomes include exploratory assessment of liver fibrosis biomarkers and lipid biomarkers.Ethics and disseminationEthical approval was granted by East of Scotland Research Ethics Service REC 1 (19/ES/0112). Results will be disseminated through peer-reviewed journals and presented at local, national and international meetings and conferences. The findings of this trial will lay the foundation for a future definitive RCT by informing trial design and optimising the intervention diets, instruments and procedures.Trial registration numberISRCTN93410321.

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Section: Open Accessmentioning

confidence: 99%

Nutrigenetics-based intervention approach for adults with non-alcoholic fatty liver disease (NAFLD): study protocol for a randomised controlled feasibility trial

et al. 2021

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“…In addition to genetic predisposition, change in lifestyles and dietary habits increases the prevalence of obesity, diabetes mellitus, metabolic syndrome, cardiovascular disease and their consequences such as NAFLD throughout the world [ 7 – 9 ]. The long-term excessive food intake and dietary composition in food groups, macronutrients and micronutrients is associated with progression of NAFLD mostly recognized by abnormal ultrasonography (US) findings or elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations as markers of liver injury [ 10 , 11 ]. In general, lower antioxidant consumption, higher intake of calorie, carbohydrate, protein and high dietary cholesterol stimulate hepatic lipid accumulation leading to development of fatty liver disease [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Dietary recommendation should be appropriate according to an individual status and even genetic background [ 20 ]. Several studies mostly in animal models introduced diet as a potent modifier of NAFLD-related genes expression [ 10 ]; for example enhanced ω-6/ω-3 poly unsaturated fatty acids (PUFAs) ratio interacts with PNPLA3 rs738409 gene in the GG homozygote and enhances ALT concentrations and hepatic fat accumulation in human [ 21 ]. Other studies also revealed the role of ω-3 fatty acids as regulators of hepatic gene expression by mainly aiming the transcription factors sterol regulatory element binding transcription factor 1 (SREBP-1c) and down-regulating inflammatory genes [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Major components of metabolic syndrome and nutritional intakes in different genotype of UCP2 −866G/A gene polymorphisms in patients with NAFLD

et al. 2016

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BackgroundIt has been suggested that dietary modifications in combination with genetic predisposition play an important role in the pathogenesis of NAFLD. In the current study we aimed to investigate the major components of metabolic syndrome in patients with non-alcoholic fatty liver disease (NAFLD) and nutritional intakes according to different genotype of uncoupling protein-2 (UCP2) −866G/A gene polymorphism in these patients.MethodsIn this study 151 participants including 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi-quantitative food-frequency questionnaire. Physical activity was obtained by metabolic equivalent questionnaire. Anthropometric assessments were conducted by a trained researcher and body mass index and waist to hip ratio were calculated. Body composition was measured by bioelectrical impedance analysis and biochemical assays including fasting serum glucose, liver enzymes and lipid profiles were measured. Polymorphisms of −866G/A UCP2 gene was determined using polymerase chain reaction-restriction fragment length polymorphism method.ResultsSerum triglyceride concentrations in 53.3 % of NAFLD patients compared with 35.5 % of control group was more than 150 mg/dl (P = 0.034). A significantly higher prevalence of low serum high density lipoprotein cholesterol concentrations was also observed in female NAFLD patients (P < 0.001). Dietary intakes in NAFLD group were not significantly different compared with control group (P > 0.05). However, according to genotypes patients with AG genotype had significantly higher protein consumption compared with control group (P < 0.05). Significantly higher consumption of dietary iron and copper in NAFLD patients with AG genotype was only observed among patients with NAFLD. However, the comparison of macro and micronutrient intakes in control group sound for stronger differences for AA genotype although these differences did not achieve significant threshold.ConclusionsA high prevalence of metabolic abnormalities was reported among NAFLD patients. Additionally, among NAFLD group, patients with AG genotype significantly consumed more protein, iron and copper in their usual diet.

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“…Genetic polymorphism and nutrition intake are involved in NAFLD progression as a multifactorial disease (Kalafati et al 2014;Moore 2010). Dietary composition can be a major factor to influence by altering the relative sources of hepatic fat accumulation (Utzschneider and Kahn 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluating −238 G>A Polymorphism Association in TNF-α Gene with Metabolic Parameters and Nutritional Intakes Among the Iranian NAFLD Patients

et al. 2016

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Different studies have shown that -238 G>A polymorphism in promoter region of tumor necrosis factor alpha (TNF-α) gene is associated with increased risk of non-alcoholic fatty liver disease (NAFLD). The current study investigates the association between metabolic parameters and nutritional intakes with -238 G>A of TNF-α promoter gene polymorphism among the Iranian patients with NAFLD. In this study, 75 patients with NAFLD and 76 individuals as control were enrolled. Dietary intakes were assessed using a semi-quantitative food-frequency questionnaire. Body mass index and waist to hip ratio were calculated. Biochemical assays were measured after 12 h fasting. -238 G>A Polymorphism of TNF-α gene was determined by using sequencing method. We observed no significant difference in frequency of different genotypes of this polymorphism between NAFLD and control groups (P > 0.05). Among biochemical parameters, TAC showed significant decrease in NAFLD patients with GG genotype when compared to controls (P = 0.001). The comparison of macro and micronutrient intakes between groups according to genotypes showed no statistically significant difference (P > 0.05). Although the data were not statistically significant, further studies with larger sample size are needed to determine the effect of dietary compounds in NAFLD.

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The Genetics of Nonalcoholic Fatty Liver Disease: Role of Diet as a Modifying Factor

Cited by 6 publications

References 140 publications

Nutrigenetics-based intervention approach for adults with non-alcoholic fatty liver disease (NAFLD): study protocol for a randomised controlled feasibility trial

Nutrigenetics-based intervention approach for adults with non-alcoholic fatty liver disease (NAFLD): study protocol for a randomised controlled feasibility trial

Major components of metabolic syndrome and nutritional intakes in different genotype of UCP2 −866G/A gene polymorphisms in patients with NAFLD

Evaluating −238 G>A Polymorphism Association in TNF-α Gene with Metabolic Parameters and Nutritional Intakes Among the Iranian NAFLD Patients

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