The Fto Gene Variant Is Associated With Myocardial Infarction In Patients With Type 2 Diabetes: A Go-Darts Study

Background: The common rs9939609 variant of the FTO gene predicts both body fat and consequently type 2 diabetes (T2D) susceptibility. We hypothesized that this variant might be associated with other metabolic phenotypes, and independently with increased risk of cardiovascular morbidity and mortality. Methods and Results: We studied the cardiovascular and lipid phenotype of the FTO variant in 2560 patients with T2D in the prospective Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS), where the rare allele frequency was 42.2%. At baseline, in a dominant model, FTO genotype was significantly associated with lower plasma HDL cholesterol (mean difference 0.05 mmol.L −1 , p=0.0008), higher triglycerides (mean difference 0.2 mmol.L −1 , p=0.007), and higher total cholesterol/HDL cholesterol ratio (mean difference 0.22, p=0.001). As previously reported FTO genotype was associated with increased BMI (mean difference 0.67 kg.m −2 , p=0.0026). After a mean follow up of 4 years, FTO genotype was associated with increased risk (HR 1.32, CI 1.04 –1.69, p=0.025) of fatal and non fatal MI (total 320 events) in a dominant model, including both age and gender (Figure 1). This association remained significant after adjustment for BMI; however, the association was abolished after adjustment for HDL cholesterol and triglycerides. Conclusion: In addition to the effect of FTO variation on obesity and type 2 diabetes risk, there is also an association with an atherogenic lipid profile, an increased risk of MI and cardiovascular death. This variant may therefore contribute to more effective targeting of specific preventative therapies such as PPAR agonists.