Insulin and Insulin Receptor Gene Polymorphisms and Susceptibility to Nonalcoholic Fatty Liver Disease

Abstract

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. OBJECTIVE: Given the pivotal role of insulin resistance in NAFLD, we hypothesized that insulin (INS) and insulin receptor (INSR) gene polymorphisms may be associated with NAFLD risk. METHODS: A total of 312 subjects, including 153 cases with biopsy-proven NAFLD and 159 controls were enrolled in this case-control study. Four polymorphisms in INS (rs3842752, rs689) and INSR (rs1052371, rs1799817) genes were genotyped using PCR-RFLP method. RESULTS: The cases with NAFLD were older and had higher BMI, systolic blood pressure, diastolic blood pressure, as well as higher serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase than the controls (P<0.001). The “TT” genotype of INSR rs1799817 compared with “CC” genotype occurred more frequently in the controls than the cases with NAFLD and the difference remained significant after adjustment for confounding factors (P=0.018; OR=0.10, 95%CI=0.02-0.76). However, no significant difference was found for INS rs3842752, INS rs689, and INSR rs1052371 gene polymorphisms between the cases with NAFLD and the controls either before or after adjustment for the confounders. CONCLUSION: These findings corroborate the hypothesis that genetic polymorphisms related to insulin resistance play a role in NAFLD susceptibility. Specifically, the INSR rs1799817 “TT” genotype had a protective effect for NAFLD. However, our results remain to be validated in other studies.

Potential role of gut microbiota-LCA-INSR axis in high fat-diet-induced non-alcoholic fatty liver dysfunction: From perspective of radiation variation

“…Liver injuries induced by LCA treatment include the impacts on signaling pathways associated with inflammation and the proliferation of G protein-coupled receptor (TGR5)-dependent signaling ( Klindt et al, 2019 ). Genetic polymorphisms related to insulin resistance will increase NAFLD susceptibility ( Nobakht et al, 2020 ). Consistent with previous reports, we found that LCA promoted H-L + HFD-induced liver dysfunction through the activation of the INSR signaling pathway.…”

Effect of the INSR gene variants on the long-term response to a 31-month childhood obesity intervention

“…Individuals with hypothyroidism may experience symptoms of decreased metabolic rate such as obesity. Another case-control study [23] found that rs1799817 (which has a strong linkage disequilibrium with rs11883325 in the CHB population (r 2 = 0.8)) was associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is a metabolic stress liver disease closely related to insulin resistance, and patients usually have metabolic syndrome such as obesity.…”

Resistin Gene Polymorphism and Nonalcoholic Fatty Liver Disease Risk

“…The increased levels of liver enzymes are also much lower in the NAFLD patients without IR than those with IR (10) . Previous reports have also shown that in addition to insulin (INS), insulin receptor (INSR), insulin receptor substrates (IRSs), insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) are all involved in IR and insulin signaling pathway (11) ; and it is interesting that significant associations have been found between NAFLD risk and INSR, IRS2, IGF1, and GHRL gene polymorphisms (12)(13)(14)(15)(16)(17) .…”