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oai:repisalud.isciii.es:20.500.12105/65182024-11-28T17:48:20Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16961col_20.500.12105_16967col_20.500.12105_16983

00925njm 22002777a 4500 dc Corella, Dolores author Sorli, Jose V. author Gonzlez, Jose I. author Ortega, Carolina author Fit, Montserrat author Bull, Monica author Martinez-Gonzalez, Miguel Angel author Ros, Emilio author Ars, Fernando author Lapetra, Jose author Gmez-Gracia, Enrique author Serra-Majem, Lluis author Ruiz-Gutierrez, Valentina author Fiol, Miquel author Coltell, Oscar author Vinyoles, Ernest author Pinto, Xavier author Marti, Amelia author Saiz, Carmen author Ordovas, Jose M author Estruch, Ramn author 2014 Background: 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. Methods: 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. Results: 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. Conclusions: 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. Cardiovasc Diabetol. 2014; 13(1):5 10.1186/1475-2840-13-5 1475-2840 Cardiovascular Diabetology http://hdl.handle.net/20.500.13003/11368 24393375 http://hdl.handle.net/20.500.12105/6518 Heart rate FAIM2 Apoptosis BODY-MASS INDEX GENOME-WIDE ASSOCIATION CORONARY-ARTERY-DISEASE CARDIOVASCULAR-DISEASE JAPANESE POPULATION MEDITERRANEAN DIET CAUSE MORTALITY SOLUBLE FAS VARIANTS LOCI 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