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Review
. 2021 Nov 15;13(11):4077.
doi: 10.3390/nu13114077.

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

José Ignacio Martínez-Montoro  1   2 , Isabel Cornejo-Pareja  3   4 , Ana María Gómez-Pérez  1 , Francisco J Tinahones  1   2   3   4
Affiliations
Review

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

José Ignacio Martínez-Montoro et al. Nutrients. .

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.

Keywords: bariatric surgery; dietary intervention; gene polymorphism; gene-nutrient interactions; non-alcoholic fatty liver disease; pharmacotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The role of PNPLA3 rs738409 C > G variant in NAFLD. PNPLA3 I148M is associated with NAFLD development and progression, and the interplay between this variant and environmental factors, including dietary habits, seems to be crucial in the pathophysiology of the disease. PNPLA3 I148M presence may also be related to an increased response to lifestyle interventions, bariatric surgery and certain types of therapeutic agents, such as the combination of sodium-glucose cotransporter 2 inhibitors and polyunsaturated fatty acid (PUFA). PNPL3: patatin-like phospholipase domain-containing protein 3; I148M (rs738409 C > G): isoleucine to methionine exchange at the amino acid position 148 due to cytosine to guanine transversion in rs738409); NAFLD: non-alcoholic fatty liver disease.
See this image and copyright information in PMC

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