Impact of Genetic Polymorphism on Response to Therapy in Non-Alcoholic Fatty Liver Disease

Abstract

In the last decades, the global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions with derived major health and socioeconomic consequences; this tendency is expected to be further aggravated in the coming years. Obesity, insulin resistance/type 2 diabetes mellitus, sedentary lifestyle, increased caloric intake and genetic predisposition constitute the main risk factors associated with the development and progression of the disease. Importantly, the interaction between the inherited genetic background and some unhealthy dietary patterns has been postulated to have an essential role in the pathogenesis of NAFLD. Weight loss through lifestyle modifications is considered the cornerstone of the treatment for NAFLD and the inter-individual variability in the response to some dietary approaches may be conditioned by the presence of different single nucleotide polymorphisms. In this review, we summarize the current evidence on the influence of the association between genetic susceptibility and dietary habits in NAFLD pathophysiology, as well as the role of gene polymorphism in the response to lifestyle interventions and the potential interaction between nutritional genomics and other emerging therapies for NAFLD, such as bariatric surgery and several pharmacologic agents.

Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease

“…Although several gene polymorphisms affect the severity of NAFLD histology [8,14,15], to the best of our knowledge, only patatin-like phospholipase domain-containing protein 3 has so far been linked to increased total mortality [16,17], with conflicting reports [11]. Thus, it is interesting that in our cohort, PXR rs7643645 GG was associated with a worse overall prognosis in NAFLD patients.…”

The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties

“…Emerging evidence suggests a variety of inherited factors, especially single-nucleotide polymorphisms (SNPs) may potentiate the susceptibility of individual regarding the development and progression as well as therapeutic response in the context of NAFLD (Ref. 66). However, no association was observed between FNDC5 rs3480 and anthropometric, metabolic and biochemical indices on the basis of 593 liver biopsy-confirmed NAFLD participants compared to healthy controls (Ref.…”

Ensayo clínico comparativo de dos dietas hipocalóricas: dieta con patrón Mediterráneo, frente a dieta hipograsa en pacientes con esteatosis hepática metabólica (EHMET). Papel del polimorfismo PNPLA3 en la respuesta a la dieta.

“…Es importante recordar que otros factores, como la AF o el consumo de alcohol, también pueden influir en la respuesta a la dieta en pacientes con EHMET. Además, parece estar relacionada con una mayor respuesta a las intervenciones en el estilo de vida, la cirugía bariátrica y ciertos tipos de agentes terapéuticos, como la combinación de inhibidores del cotransportador de sodio-glucosa y AGPI (141).…”