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

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 di...

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Detalles Bibliográficos
Autores: Corella, Dolores, Sorli, Jose V., Gonzlez, Jose I., Ortega, Carolina, Fit, Montserrat, Bull, Monica, Martinez-Gonzalez, Miguel Angel, Ros, Emilio, Ars, Fernando, Lapetra, Jose, Gmez-Gracia, Enrique, Serra-Majem, Lluis, Ruiz-Gutierrez, Valentina, Fiol, Miquel, Coltell, Oscar, Vinyoles, Ernest, Pinto, Xavier, Marti, Amelia, Saiz, Carmen, Ordovas, Jose M, Estruch, Ramn
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6518
Acceso en línea:http://hdl.handle.net/20.500.12105/6518
Access Level:acceso abierto
Palabra clave: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
Dieta Mediterránea
Predisposición Genética a la Enfermedad
Femenino
Infarto del Miocardio
Proteínas de la Membrana
Masculino
Estudios de Seguimiento
Alelos
Factores de Riesgo
Estudios Longitudinales
Frecuencia Cardíaca
Humanos
Persona de Mediana Edad
Obesidad
Estudios de Asociación Genética
Anciano
Diabetes Mellitus Tipo 2
Proteínas Reguladoras de la Apoptosis
Polimorfismo Genético
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Aged
Alleles
Follow-Up Studies
Heart Rate
Humans
Middle Aged
Obesity
Longitudinal Studies
Membrane Proteins
Myocardial Infarction
Male
Female
Risk Factors
Diet, Mediterranean
Genetic Association Studies
Apoptosis Regulatory Proteins
Polymorphism, Genetic
Descripción
Sumario: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.

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