Preliminary Evidence of FABP2 A54T Polymorphism Associated with Reduced Risk of Type 2 Diabetes and Obesity in Women from a German Cohort

Abstract

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.

Influence of ALA54THR Polymorphism of Fatty Acid-binding Protein 2 on Obesity and Cardiovascular Risk Factors

“…In our study dietary intake did not show statistical differences between groups, in this way our data have been controlled by dietary intake and previous discrepancies could be explained by this uncontrolled factor (dietary intake). In our study, the elevation of infl ammation markers (CRP and IL-6) in patients with Thr allele could be related with an altered postprandial response of fatty acids absorption (not measured in our design) [37] . Elevated free fatty acids increases the accumulation of triglycerides in the adipocyte, related with imbal-ance of lipoprotein lipase activity and overproduction of adipokines such as IL-6.…”

Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies

“…FABP2 (fatty acid binding protein 2) is an intracellular proteins expressed only in the intestine and involved in the absorption and intracellular transport of dietary long-chain fatty acids. The association of FABP2 with both 2DM and obesity has been reported by several studies [30-33]. Previous reports showed that the variants of FABP2 increased flux of dietary fatty acids into the circulation, and was also associated with increased fasting inculin concentration, fasting fatty acid oxidation and reduced glucose uptake, all are etiology of metabolic disorders [34].…”

Polymorphisms in fatty acid binding protein 5 show association with type 2 diabetes

“…Furthermore, the Ala54Thr SNP was associated with obesity but not T2DM in a study of Greek volunteers (47). However, in a German cohort, the Thr54 carriers were associated with a lower risk of T2DM and obesity in women (48). Our findings showing that the FABP2 Ala54Thr SNP exhibits a significant association with T2DM in HA agrees with a previous study performed in Chilean older adults (49).…”