Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects

Increase in arterial stiffness is associated with aging, which is improved by regular exercise. Endothelin ( ET) system has crucial roles in regulating vascular tone and in the progression of atherosclerosis. We hypothesized that molecular variations ( ie, gene polymorphisms) in ET- related gene might affect exercise- induced improvement in arterial stiffness with age in human subjects. The present study provides a cross- sectional investigation of 191 healthy middle- aged and older ( 65 +/- 1 years) human subjects to clarify the relationship between the regular exercise- induced improvement of arterial stiffness and the gene polymorphisms of ET converting enzyme ( ECE)- 1, ECE- 2, ET- A receptor ( ET- A), and ET- B receptor ( ET- B). The study subjects were divided into active and inactive groups based on the median value ( 186 kcal/ d) of energy expenditure. Brachial- ankle arterial pulse wave velocity ( baPWV) was used to evaluate arterial stiffness. All individuals were genotyped for 4 different polymorphisms of the ET system: 2013( + 289) A/ G in intron 17 of ECE- 1, 669( + 17) T/ C in intron 5 of ECE- 2, 958A/ G in exon 6 of ET- A, and 831A/ G in exon 4 of ET- B. The baseline baPWV was significantly lower in the active group without any change in blood pressure. Polymorphisms in ECE- 1 influenced basal blood pressure. Polymorphisms in ECE- 1 and ECE- 2 had no effect on baPWV between active and inactive groups. However, polymorphisms in both ET- A and ET- B affected baPWV in the 2 groups. The present results suggest that differences in ET- A and ET- B polymorphisms may influence the response of the vascular wall to exercise whereas ECE- 1 polymorphisms may affect basal blood pressure.