on March 30, 2009
Published online before print March 30, 2009, doi: 10.1161/CIRCGENETICS.108.822320
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Original Article |
The FTO Gene is Associated with an Atherogenic Lipid Profile and Myocardial Infarction in Patients with Type 2 Diabetes: A Go-DARTS study.
1 Diabetes Research Group, University of Dundee, Dundee, United Kingdom;
2 Population Pharmacogenetics Group, University of Dundee, Dundee, United Kingdom
3 E-mail: nuclear-receptor{at}dundee.ac.uk
Background—Common variation in the Fat Mass and Obesity related (FTO) gene is associated with increased body fat and susceptibility to type 2 diabetes (T2D). We hypothesized that this would also associate with metabolic phenotypes of insulin resistance, and increased risk of cardiovascular morbidity and mortality.
Methods and Results&mdashFTO rs9939609 genotype was determined in 4897 patients with T2D in the prospective Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) study. The A allele was associated with lower plasma HDL cholesterol (mean difference 0.03 mmol/L, p=0.008), higher triglycerides (0.1 mmol/L, p=0.007), higher atherogenic index of plasma (0.03, p=0.003) and, as expected, increased BMI (0.77 kg/m2, p=8.8x10-6). During a mean follow up of 3.6 years the A allele was also associated with increased risk (HR 2.36, CI 1.49-3.74, p=0.0002) of fatal and non fatal myocardial infarction (total 324 events) in a model including baseline age, gender, prevalent myocardial infarction, smoking status, statin and insulin use. This association diminished but remained significant when obesity related traits such as BMI, glycated haemoglobin and lipid parameters were also included (HR 2.01 CI 1.18-3.45, p=0.011). There was a strong interaction of FTO genotype and statin use and cardiovascular outcome (p=0.001) such that cardiovascular morbidity and mortality was completely abrogated in individuals prescribed statins.
Conclusion—The increased fat mass in carriers of the A allele of rs9939609 of FTO is associated not only with increased risk of T2D, but also with an increase in atherogenic lipid profile, and myocardial infarction in these patients. This variant may therefore in future contribute to more effective targeting of specific preventative therapy.
Key Words: diabetes mellitus • genetics • heart diseases • metabolism • myocardial infarction
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