Genetic Variations of AKT1 are Associated with Risk Screening for Non-Alcoholic Fatty Liver Disease

Abstract

Purpose

Protein kinase B (PKB/AKT) has shown a high profile in the research of metabolic diseases. This research sought to determine whether the AKT1 gene’s single nucleotide polymorphisms (SNPs) and the risk of developing non-alcoholic fatty liver disease (NAFLD) were related.

Patients and Methods

Recruited in this case–control study were 2693 subjects, including 815 with NAFLD and 1878 without NAFLD. Three SNPs of AKT1 (rs2494732, rs2494752 and rs1130233) were genotyped. To examine the correlation between SNPs and NAFLD susceptibility, logistic regression was performed.

Results

After adjusting for sex, age, triglyceride and glucose, AKT1 rs2494732-C (all P < 0.05 in co-dominant model, dominant model and additive model) and rs2494752-G ( P < 0.05 in co-dominant model) were linked to a lower risk of NAFLD. The combined effect of both SNPs on NAFLD risk was statistically significant, showing a dose dependence ( P _trend = 0.010). Sex, body mass index, hypertension, hyperglycemia, hypertriglyceridemia, high-density lipoprotein-cholesterol, alanine aminotransferase, and beneficial alleles were all significant predictors of NAFLD risk (all P < 0.05). The prediction model achieved good discrimination, with an area under the receiver operating characteristic curve of 0.779. The Hosmer–Lemeshow test suggested an inadequate calibration of the model ( χ ² = 21.073, P = 0.007).

Conclusion

AKT1 rs2494732 and rs2494752 may be related to Chinese NAFLD susceptibility. The prediction model combining both SNPs with clinical factors displays a strong ability to discriminate NAFLD patients. Both SNPs may be exploited to design new models for early screening of NAFLD high-risk population.

Graphical Abstract