Genetic background in nonalcoholic fatty liver disease: A comprehensive review.
In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.
Fabio Salvatore Macaluso, Marcello Maida, Salvatore Petta, Section of Gastroenterology, DIBIMIS, University of Palermo, 90127 Palermo, Italy.
Fabio Salvatore
FS
Macaluso
Fabio Salvatore Macaluso, Marcello Maida, Salvatore Petta, Section of Gastroenterology, DIBIMIS, University of Palermo, 90127 Palermo, Italy.
Marcello
M
Maida
Fabio Salvatore Macaluso, Marcello Maida, Salvatore Petta, Section of Gastroenterology, DIBIMIS, University of Palermo, 90127 Palermo, Italy.
Salvatore
S
Petta
D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D040941:Heredity; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors
D005819:Genetic Markers
Candidate gene studies; Genetics; Genome-wide association studies; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Patatin-like phospholipase domain-containing 3; Transmembrane 6 superfamily member 2