Significance of genetic polymorphisms in patients with nonalcoholic fatty liver disease

Abstract

Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC). Among these genetic polymorphisms, many studies and meta-analyses have demonstrated that position 148 (rs738409 C/G) of the patatin-like phospholipase domain-containing protein (PNPLA3) is a genetic factor associated with NAFLD pathophysiological features, such as hepatic fat level, hepatic inflammation, fibrosis, and HCC. However, the impact of genetic polymorphisms on NAFLD pathophysiology appears to differ among ethnic groups. Therefore, further studies with larger sample sizes are needed for each ethnic group.

MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients

“…Our finding is in agreement with Bernard et al; Hussain et al; Peng et al; Zheng et al; Miyaaki and Nakao who reported that MTP -493G/T polymorphism may be used for early detection of NAFLD. 16 , 12 , 2 , 36 , 37 This might appear in contrast with a study in a Brazilian population which showed that there was no significant association between the MTP -493G/T polymorphism and NAFLD, 20 as well as Marra who demonstrated that, the frequency of the G allele or of the G/G genotype for MTP was not different from that of controls without fatty liver. 38 …”

Role of the PNPLA3 polymorphism rs738409 on silymarin + vitamin E response in subjects with non-alcoholic fatty liver disease

“…The significant increase in serum glucose levels and the HOMA insulin resistance index at the end of treatment only in NAFLD patients with PNPLA3 G-allele is an intriguing finding. Perhaps, it may be due to an adverse effect of vitamin E supplementation (36) or an unknown interaction of this polymorphism with glucose metabolism. In our study, patients with the I148M PNPLA3 variant (G-allele carriers) had lower NASH resolution values.…”

“…Thirdly, the small sample size and the unicenter pilot study has limited the generalization of our results. Finally, our pilot study was only performed in Caucasians and ethnicity could be an unknown factor that influences this association (36).…”

Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights

“…Aside from dietary models, there are multiple genetic mouse models used to mimic NAFL/NASH; such as, ob/ob mice (mutation in the leptin gene), db/db mice (mutation in the leptin receptor gene), and foz/foz mice (mutation in Alms1 gene, essential for primary ciliary function) 76 . In humans, there are certain genetic polymorphisms that are strongly associated with susceptibility to NAFL/NASH; such as, mutations in genes encoding for lipid metabolism, glucose metabolism, hypertension, or inflammation 77 . However, it is important to note that the genetic mouse models of NAFL/NASH do not overlap with these genetic polymorphisms.…”