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

Area of Science:

• Genetics and Molecular Biology
• Metabolic Diseases
• Hepatology

Background:

• Protein kinase B (PKB/AKT) pathway is crucial in metabolic disease research.
• Non-alcoholic fatty liver disease (NAFLD) is a growing health concern.
• Understanding genetic predispositions to NAFLD is essential for early intervention.

Purpose of the Study:

• To investigate the association between single nucleotide polymorphisms (SNPs) in the AKT1 gene and the risk of developing NAFLD.
• To identify specific AKT1 SNPs that may influence NAFLD susceptibility.
• To evaluate the predictive value of AKT1 SNPs in combination with clinical factors for NAFLD risk.

Main Methods:

• A case-control study involving 2693 participants (815 NAFLD, 1878 controls).
• Genotyping of three AKT1 SNPs: rs2494732, rs2494752, and rs1130233.
• Logistic regression analysis was employed to assess the correlation between SNPs and NAFLD risk, adjusting for relevant clinical variables.

Main Results:

• The AKT1 rs2494732-C and rs2494752-G variants were significantly associated with a lower risk of NAFLD.
• A combined analysis of these two SNPs demonstrated a statistically significant, dose-dependent protective effect against NAFLD.
• A prediction model incorporating these SNPs and clinical factors showed good discriminatory ability (AUC = 0.779), though calibration was suboptimal.

Conclusions:

• Specific AKT1 SNPs (rs2494732 and rs2494752) may play a role in the susceptibility to NAFLD in the Chinese population.
• The developed prediction model, integrating genetic and clinical data, shows promise for identifying individuals at high risk for NAFLD.
• These genetic markers offer potential for novel strategies in the early screening and prevention of NAFLD.