title: 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.
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.
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain. dolores.corella@uv.es.
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Jose V
authors.initials: JV
authors.lastname: Sorlí
authors.forename: José I
authors.initials: JI
authors.lastname: González
authors.forename: Carolina
authors.initials: C
authors.lastname: Ortega
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fitó
authors.forename: Monica
authors.initials: M
authors.lastname: Bulló
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martínez-González
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.forename: Fernando
authors.initials: F
authors.lastname: Arós
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
authors.forename: Lluís
authors.initials: L
authors.lastname: Serra-Majem
authors.forename: Valentina
authors.initials: V
authors.lastname: Ruiz-Gutierrez
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.forename: Oscar
authors.initials: O
authors.lastname: Coltell
authors.forename: Ernest
authors.initials: E
authors.lastname: Vinyoles
authors.forename: Xavier
authors.initials: X
authors.lastname: Pintó
authors.forename: Amelia
authors.initials: A
authors.lastname: Martí
authors.forename: Carmen
authors.initials: C
authors.lastname: Saiz
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
mesh_terms: D000368:Aged; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000453:epidemiology / Q000235:genetics*; D038441:Diet, Mediterranean; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000178:diet therapy / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000178:diet therapy / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; C400427:FAIM2 protein, human; D008565:Membrane Proteins