Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial

Identifier:  imarina:831546

Handle: https://hdl.handle.net/20.500.11797/imarina831546

Authors:  Corella, Dolores; Sorli, Jose V; Gonzalez, Jose I; Ortega, Carolina; Fito, Montserrat; Bullo, Monica; Martinez-Gonzalez, Miguel Angel; Ros, Emilio; Ars, Fernando; Lapetra, Jose; Gomez-Gracia, Enrique; Serra-Majem, Lluis; Ruiz-Gutierrez, Valentina; Fiol, Miquel; Coltell, Oscar; Vinyoles, Ernest; Pinto, Xavier; Marti, Amelia; Saiz, Carmen; Ordovs, Jose M; Estruch, Ramon

Abstract:
The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G?>?A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains uncertain.We analyzed the association between the FAIM2-rs7138803 polymorphism and obesity, blood pressure and heart rate in 7,161 participants (48.3% with type 2 diabetes) in the PREDIMED study at baseline. We also explored gene-diet interactions with adherence to the Mediterranean diet (MedDiet) and examined the effects of the polymorphism on cardiovascular disease incidence per diabetes status after a median 4.8-year dietary intervention (MedDiet versus control group) follow-up.We replicated the association between the FAIM2-rs7138803 polymorphism and greater obesity risk (OR: 1.08; 95% CI: 1.01-1.16; P?=?0.011; per-A allele). Moreover, we detected novel associations of this polymorphism with higher diastolic blood pressure (DBP) and heart rate at baseline (B?=?1.07; 95% CI: 0.97-1.28 bmp in AA vs G-carriers for the whole population), that remained statistically significant even after adjustment for body mass index (P?=?0.012) and correction for multiple comparisons. This association was greater and statistically significant in type-2 diabetic subjects (B?=?1.44: 95% CI: 0.23-2.56 bmp; P?=?0.010 for AA versus G-carriers). Likewise, these findings were also observed longitudinally over 5-year follow-up. Nevertheless, we found no statistically significant gene-diet interactions with MedDiet for this trait. On analyzing myocardial infarction risk, we detected a nominally significant (P?=?0.041) association in type-2 diabetic subjects (HR: 1.86; 95% CI:1.03-3.37 for AA versus G-carriers), although this association did not remain statistically significant following correction for multiple comparisons.We confirmed the FAIM2-rs7138803 relationship with obesity and identified novel and consistent associations with heart rate in particular in type 2 diabetic subjects. Furthermore, our results suggest a possible association of this polymorphism with higher myocardial infarction risk in type-2 diabetic subjects, although this result needs to be replicated as it could represent a false positive.