Angiotensinogen M235T polymorphism associates with exercise hemodynamics in postmenopausal women

Abstract

.-We sought to determine whether the M235T angiotensinogen (AGT) polymorphism, either interacting with habitual physical activity (PA) levels or independently, was associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. Sixty-one healthy postmenopausal women (16 sedentary, 21 physically active, and 24 endurance athletes) had heart rate (HR), blood pressure (BP), cardiac output, stroke volume (SV), total peripheral resistance (TPR), and arteriovenous O 2 difference (a-vDO2) assessed during 40, 60, 80, and ϳ100% of VO 2 max treadmill exercise. VO 2 max did not differ among AGT genotype groups; however, maximal HR was 14 beats/min higher in AGT TT than MM genotype women (P Ͻ 0.05). AGT TT genotype women also had 19 beats/min higher HR during ϳ100% VO 2 max exercise than AGT MM genotype women (P ϭ 0.008). AGT genotype also interacted with habitual PA levels to associate with systolic BP and a-vDO 2 during ϳ100% VO2 max exercise (both P Ͻ 0.01). AGT TT genotype women had 11 beats/min higher HR during submaximal exercise than MM genotype women (P Ͻ 0.05). AGT genotype interacted with habitual PA levels to associate with systolic BP during submaximal exercise (P ϭ 0.009). AGT genotype, independently or interacting with habitual PA levels, did not associate significantly with diastolic BP, cardiac output, SV, or TPR during maximal or submaximal exercise. Thus this common genetic variant in the renin-angiotensin system appears to associate, both interactively with habitual PA levels and independently, with HR, systolic BP, and a-vDO 2 responses to maximal and submaximal exercise in postmenopausal women. heart rate; blood pressure; cardiac output; stroke volume; genetics THE RENIN-ANGIOTENSIN-ALDOSTERONE system is intimately involved in the regulation of blood pressure (BP) and cardiovascular (CV) hemodynamics through its effects on angiotensin II, a potent vasoconstrictor, and fluid and electrolyte balance. A common genetic polymorphism within the renin-angiotensin-aldosterone system, a T-for-C substitution at nucleotide 704 of the angiotensinogen (AGT) gene leading to a methionine-to-threonine substitution at codon 235 in some but not all studies, has been associated with hypertension and BP (2, 5, 10, 13, 23). This variant is especially appealing as a candidate locus that might affect CV hemodynamics because it is relatively common (15). Furthermore, it has been shown to affect plasma angiotensinogen levels (11), which are normally close to the K m for the conversion of angiotensinogen to angiotensin I by renin (6). Therefore, changes in angiotensinogen levels could potentially alter angiotensin I and II levels. Thus the AGT locus would appear to be a putative candidate locus that might affect CV hemodynamics.Previously Krizanova and coworkers (14) assessed the association of BP and heart rate (HR) during rest and submaximal exercise with AGT M235T polymorphisms. The primary aim of a second study, by Rankinen et al. (22), was to examine the association between this common genetic polymo...

NOS3 Gene Polymorphisms and Exercise Hemodynamics in Postmenopausal Women

“…Using the same women tested as in the present study, we have found other genes that were associated with HR during submaximal and maximal exercise [13,14,26]. McCole et al showed that the common angiotensinogen M235T polymorphism had a significant effect on submaximal and maximal exercise HR.…”

Genes and human elite athletic performance

“…The M235T missense polymorphism in the angiotensinogen gene AGT showed a positive association with several measures of cardiorespiratory performance in 61 healthy postmenopausal women, including 24 elite endurance athletes (McCole et al 2002), and with left ventricular mass (LVM) in two separate studies on elite endurance athletes: a highly significant association in a cohort of 50 male and 30 female athletes (Karjalainen et al 1999) and a weak association in a combined analysis with genotype at the ACE I/D polymorphism in 83 male athletes (Diet et al 2001). No evidence of an association was identified in two cohorts of untrained individuals (Linhart et al 2000;Kauma et al 1998).…”

Identifying genes for primary hypertension: methodological limitations and gene–environment interactions

“…[32][33][34][35][36][37][38][39][40] Some, but not all, of these studies emanate from clinical trials of exercise, diet or drug treatment interventions on blood pressure regulation. The most widely studied gene in this context is the angiotensinogen I-converting enzyme gene (ACE).…”

“…Studies examining the modifying roles of ACE genotypes on blood pressure response to exercise have focused primarily on the effects of acute exercise often in relatively small samples. [32][33][34][35][36][37][38][39] At least two medium-to long-term clinical trials from North America 37 and Finland 40 have reported on the association between ACE genotypes and blood pressure responses to long-term aerobic exercise training. In the North American HERITAGE study, Rankinen and colleagues examined the blood pressure response by ACE I/D and M235T genotypes to an exercise stress test before and after 20 weeks of aerobic exercise training.…”