Risk Management and Healthcare Policy (Jul 2023)
Genetic Variations of AKT1 are Associated with Risk Screening for Non-Alcoholic Fatty Liver Disease
Abstract
Yajie Ding,1,* Zongzhe Tang,1,* Ru Zhang,1 Mengting Zhang,1 Qing Guan,1 Liuxin Zhang,2 Hongliang Wang,3 Yue Chen,1 Wei Zhang,4 Jie Wang1 1Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong (SAR), People’s Republic of China; 3Department of General Practice, Ninghai Road Community Health Service Center, Nanjing, Jiangsu, People’s Republic of China; 4Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Wang, Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86-25-86869557, Fax +86-25-86868501, Email [email protected]: 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 (Ptrend = 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 (χ2 = 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: Keywords: NAFLD, susceptibility, AKT1 gene, polymorphism, risk screening
