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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

Dolores Corella1221*, Jose V Sorlí12, José I González12, Carolina Ortega12, Montserrat Fitó23, Monica Bulló24, Miguel Angel Martínez-González25, Emilio Ros26, Fernando Arós27, José Lapetra28, Enrique Gómez-Gracia29, Lluís Serra-Majem102, Valentina Ruiz-Gutierrez112, Miquel Fiol122, Oscar Coltell132, Ernest Vinyoles14, Xavier Pintó152, Amelia Martí162, Carmen Saiz1, José M Ordovás171819 and Ramón Estruch220

Author Affiliations

1 Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain

2 CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain

3 Cardiovascula Risk and Nutrition Research Group, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain

4 Human Nutrition Unit, Faculty of Medicine, IISPV, University Rovira i Virgili, Reus, Spain

5 Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain

6 Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain

7 Department of Cardiology, Araba University Hospital, Vitoria, Spain

8 Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain

9 Department of Epidemiology, School of Medicine, University of Malaga, Malaga, Spain

10 Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

11 Instituto de la Grasa, Consejo Superior de Investigaciones Científicas, Sevilla, Spain

12 University Institute for Health Sciences Investigation, Hospital Son Dureta, Palma de Mallorca, Spain

13 Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Jaume I University, Castellón, Spain

14 Primary Care Division, Catalan Institute of Health, Barcelona, Spain

15 Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

16 Department of Nutrition and Physiology, Faculty of Pharmacy, University of Navarra, Pamplona, Spain

17 Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

18 IMDEA Alimentación, Madrid, Spain

19 Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

20 Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain

21 Genetic and Molecular Epidemiology Unit, Valencia University, Blasco Ibañez, 15, 46010 Valencia, Spain

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Cardiovascular Diabetology 2014, 13:5  doi:10.1186/1475-2840-13-5

Published: 6 January 2014



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.

Heart rate; FAIM2; Apoptosis