Publication: 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
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2014
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BioMed Central (BMC)
Abstract
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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MeSH Terms
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 Risk Factors Diet, Mediterranean Genetic Association Studies Apoptosis Regulatory Proteins Polymorphism, Genetic
DeCS Terms
Dieta Mediterránea Predisposición Genética a la Enfermedad Femenino Infarto del Miocardio ProteÃnas de la Membrana Masculino Estudios de Seguimiento Alelos Alelos Factores de Riesgo Estudios Longitudinales Frecuencia CardÃaca Humanos Persona de Mediana Edad Obesidad Estudios de Asociación Genética Anciano Diabetes Mellitus Tipo 2 ProteÃnas Reguladoras de la Apoptosis Polimorfismo Genético
Bibliographic citation
Cardiovasc Diabetol. 2014; 13(1):5