Genetic susceptibility to type 2 diabetes: Insights from a comprehensive meta-analysis of FABP2 polymorphisms

To investigate the association between the FABP2 (rs1799883) polymorphism and the risk of developing type 2 diabetes mellitus (T2DM) across different populations and genetic models. Type 2 diabetes mellitus (T2DM) is a multicausal condition influenced by both hereditary and environmental determinants. The FABP2 (rs1799883) polymorphism has been proposed as a potential hereditary risk factor due to its role in lipid metabolism, though previous findings across populations and genetic models remain inconsistent.

Studies sourced from PubMed, ScienceDirect, EMBASE, and other relevant databases up to June 1, 2025, were used to conduct the meta-analysis. Appropriate case-control studies examining the FABP2 polymorphism and T2DM were analyzed under four genetic models. Subgroup analysis by ethnicity, in silico functional predictions (SIFT, PolyPhen-2), and power analysis were also performed.

A total of 26 studies, including 6032 T2DM patients and 8907 controls, were analyzed. The Ala54Thr variant showed no significant association with T2DM under the allele, dominant, or overdominant models. However, a strong association was identified within the recessive model (AA vs. AT + TT; OR = 4.11, 95% CI: 2.96-5.71, P < 0.00001). Subgroup analysis revealed significant associations in Asian and Caucasian populations, while a protective effect was noted in other ethnic groups. In silico predictions indicated the variant is functionally tolerated and benign. The analysis had a high statistical power (99%).

The Ala54Thr polymorphism of the FABP2 gene is significantly associated with higher T2DM risk under a recessive model, notably in Asian and Caucasian populations. These findings support its potential utility as a genetic marker in risk assessment and highlight the importance of ethnicity-specific analysis in understanding T2DM susceptibility.