Association between functional FABP2 promoter haplotype and type 2 diabetes

Area of Science:

• Genetics and Molecular Biology
• Metabolic Diseases
• Human Physiology

Background:

• Fatty acid-binding protein 2 (FABP2) is crucial in intestinal fatty acid metabolism.
• Previous studies suggest a link between FABP2 genetic variants and type 2 diabetes (T2D).
• FABP2 promoter polymorphisms have been associated with lipid metabolism and body composition.

Purpose of the Study:

• To investigate the association between FABP2 promoter variants and the risk of type 2 diabetes mellitus.
• To explore potential interactions between FABP2 promoter haplotypes and the Ala54Thr polymorphism in T2D susceptibility.

Main Methods:

• Identified FABP2 promoter single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms in a Caucasian population.
• Defined FABP2 promoter haplotypes (A and B) based on linkage disequilibrium.
• Conducted a prospective case-control study using the EPIC-Potsdam cohort (192 T2D cases, 384 controls).
• Analyzed the association of FABP2 variants with T2D risk, adjusting for BMI and other covariates.

Main Results:

• FABP2 promoter haplotype B was significantly associated with a decreased risk of type 2 diabetes in male subjects.
• This protective effect was independent of BMI and other covariates.
• The association remained significant even after adjusting for the FABP2 Ala54Thr polymorphism, suggesting a distinct role for promoter variants.
• No association was found between FABP2 variants and BMI, body fat, leptin, HbA1c, total cholesterol, or HDL.

Conclusions:

• Functional FABP2 promoter haplotypes may play a role in type 2 diabetes pathogenesis.
• The association appears to be sex-specific, with a protective effect observed in males.
• These findings highlight the importance of genetic variations in FABP2 in the context of metabolic disease risk.