RÉSUMÉ
Atherosclerosis is a heritable trait with little known about specific genetic influences on preclinical measures of plaque formation. Based on relations of parasympathetic-cholinergic function to atherosclerosis and to a choline transporter gene [CHT1 (G/T)] polymorphism, we investigated whether the same allelic variant predicts variation in carotid intima-media thickness (IMT) and plaque formation. Carotid IMT and plaque occurrence as well as genotyping for the CHT1 (G/T) variant were measured in a sample (N = 264) of generally healthy adults (age 30-55) of European ancestry. CHT1 GG homozygotes had greater IMT (P < 0.005) and plaque occurrence (P < 0.020) than T allele carriers. This is the first study showing polymorphic variation in the CHT1 gene to predict early, subclinical measures of carotid atherosclerosis which may aid in understanding cholinergic-vagal processes potentially underlying atherosclerotic risk.
Sujet(s)
Artériopathies carotidiennes/imagerie diagnostique , Artériopathies carotidiennes/génétique , Artère carotide commune/imagerie diagnostique , Épaisseur intima-média carotidienne , Polymorphisme génétique , Symporteurs/génétique , Adulte , Maladies asymptomatiques , Artériopathies carotidiennes/ethnologie , Femelle , Fréquence d'allèle , Prédisposition génétique à une maladie , Humains , Modèles logistiques , Mâle , Adulte d'âge moyen , Odds ratio , Pennsylvanie/épidémiologie , Phénotype , Valeur prédictive des tests , Appréciation des risques , Facteurs de risque , /génétiqueRÉSUMÉ
Previous evidence suggests that the dual-specific A kinase-anchoring protein 2 functional polymorphism (AKAP10 (A/G) I646V) influences heart rate (HR) and heart rate variability (HRV) in mice and humans (N=122) with cardiovascular disease. Here, we asked whether this AKAP10 variant predicts HR and HRV in a large sample of healthy humans. Resting HR and short-term time and frequency domain measures of HRV (5 min during paced and unpaced respiration conditions) were assessed in a U.S. community sample (N=1,033) of generally healthy men and women (age 30-54) of European ancestry. Each person was genotyped for the AKAP10 variant. As with previous work, the AKAP10 Val allele predicted greater resting HR (Paced p<.01; Unpaced p<.03) and diminished HRV (Paced ps <.05) suggesting that this variant may modulate the sensitivity of cardiac pacemaker cells to autonomic inputs, possibly conferring risk for arrhythmias and sudden cardiac death.
