Nonalcoholic fatty liver disease and metabolic syndrome: Shared genetic basis of pathogenesis

Sookoian, Silvia; Pirola, Francesca

doi:10.1002/hep.28746

Cited by 39 publications

(37 citation statements)

References 10 publications

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“…Moreover, genetic co-variance assessment of metabolic syndrome (MetS)-associated traits in The Genetics of NAFLD in Twins Consortium revealed a significant association between hepatic steatosis and body mass index (BMI) and hyperinsulinemia, and between hepatic fibrosis and glycated haemoglobin (HbA1c) [18]. It is noteworthy that the available data mining strategies and systems biology approaches strongly suggest genetic commonality between NAFLD and MetS [21]. …”

Section: Nafld Is a Polygenic And Heritable Diseasementioning

confidence: 99%

“…In conclusion, while the role of genetic factors associated with the risk of NAFLD in lean patients is not fully understood, it is plausible to speculate that variants associated with the risk of type 2 diabetes or insulin resistance [21,60], as well as variants in the mitochondrial DNA, are involved [60]. At any rate, it is reasonable to assume that rs738409, which is not associated with either obesity or type 2 diabetes [35], has no differential influence in the genetic risk of NAFLD in lean individuals.…”

Section: The Genetic Susceptibility In Lean Nafldmentioning

confidence: 99%

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Genetic predisposition in nonalcoholic fatty liver disease

2017

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.

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Section: Nafld Is a Polygenic And Heritable Diseasementioning

confidence: 99%

Section: The Genetic Susceptibility In Lean Nafldmentioning

confidence: 99%

Genetic predisposition in nonalcoholic fatty liver disease

2017

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“…However, at present, the exact pathogenesis of NAFLD is still not completely clear. Currently, NAFLD is deemed to be the liver manifestation of MetS . Genetic factors and environmental exposures are considered to contribute to the development of NAFLD .…”

Section: Introductionmentioning

confidence: 99%

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta‐analysis of observational studies

Zhou

Yang

et al. 2019

Helicobacter

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Background The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta‐analysis to elucidate the association. Methods A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random‐effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test. Results Fifteen studies (eleven cross‐sectional, two case‐control, and two cohort studies) were included in this meta‐analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11‐1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37‐23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected. Conclusions Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them.

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“…Considered jointly, the aforementioned evidence suggests the existence of shared pathogenic mechanisms between NAFLD and Metabolic syndrome‐associated diseases . Hence, this imparts the challenge of designing and implementing treatment strategies for simultaneously targeting multiple phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Review article: shared disease mechanisms between non‐alcoholic fatty liver disease and metabolic syndrome – translating knowledge from systems biology to the bedside

Sookoian

Pirola

2019

Aliment Pharmacol Ther

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Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Characterised by abnormal fat accumulation in the liver, NAFLD presents high degree of comorbidity with disorders of the metabolic syndrome, including type 2 diabetes, obesity and cardiovascular disease. These comorbidities have strong negative impact on the natural course of NAFLD and vice versa, whereby the presence of NAFLD substantially modifies the course and prognosis of metabolic syndrome-associated diseases.Aim: To use systems biology strategies to interrogate disease mechanisms that are common to NAFLD and metabolic syndrome. Methods:We mapped shared gene/protein-disease interaction networks, we performed gene-disease enrichment analysis to assess pleiotropy, and we created a genedrug connectivity network. Results:We found that a shared network of genes/proteins is overrepresented by immune response-related pathways, post-translational modifications of nuclear receptors, and platelet-related processes, including activation and platelet signalling.Likewise, gene-based disease-enrichment analysis suggested underlying molecular effectors that are shared with major systemic disorders, including diverse autoimmune diseases, kidney, respiratory and nervous system disorders, cancer and infectious diseases. The shared list of genes/proteins was enriched in drug targets for anti-inflammatory therapy, drugs used to treat cardiovascular diseases, antimicrobial agents and phytochemicals, among many other approved pharmaceutical compounds. By leveraging on publicly available OMICs data, we were able to show that shared loci are not necessarily affected by reverse causality. Conclusion:We provide evidence indicating that NAFLD treatment, including severe histological traits, cannot be limited to the use of a single drug, as it rather requires a multi-target therapeutic approach.

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Nonalcoholic fatty liver disease and metabolic syndrome: Shared genetic basis of pathogenesis

Cited by 39 publications

References 10 publications

Genetic predisposition in nonalcoholic fatty liver disease

Genetic predisposition in nonalcoholic fatty liver disease

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta‐analysis of observational studies

Review article: shared disease mechanisms between non‐alcoholic fatty liver disease and metabolic syndrome – translating knowledge from systems biology to the bedside

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