NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training

Abstract

. NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training. J Appl Physiol 99: 1905-1911, 2005. First published July 7, 2005 doi:10.1152/japplphysiol.00380.2005.-Systemic oxidative stress plays a role in many degenerative diseases. Although regular physical activity has been known as the most effective nonpharmacological intervention to alleviate the oxidative stress, the beneficial effect varies between individuals. We investigated whether NADPH oxidase p22phox gene C242T and A640G polymorphisms are associated with systemic oxidative stress level response to exercise training (ExTr). Fifty-nine sedentary middle-aged to older Caucasians with relatively high cardiovascular disease risk factors underwent a 6-mo standardized ExTr program. Body mass index, plasma lipoprotein-lipid profiles, cardiovascular fitness, and plasma thiobarbituric acid reactive substances (TBARS) were measured before and after ExTr. Demographic and initial levels of cardiovascular disease risk factors were similar among genotype groups for both polymorphisms. Overall, TBARS was decreased by 16% with ExTr in the entire group (P Ͻ 0.001). There was no significant difference in TBARS changes with ExTr among the C242T genotype groups. However, A allele carriers showed greater reduction in TBARS than noncarriers at the A640G locus (P ϭ 0.05). There was a significant interaction (P ϭ 0.05) between ExTr and A640G polymorphism in TBARS changes with ExTr. This interaction remained after accounting for age and baseline TBARS level. Furthermore, diplotype analysis showed that TBARS was decreased to a greater extent in the C242/A640 haplotype carriers compared with the noncarriers (P Ͻ 0.05). We found that p22phox polymorphisms, especially A640G, were associated with differential changes in systemic oxidative stress with aerobic exercise training. gene polymorphisms; haplotype; lipid peroxidation OXIDATIVE STRESS PLAYS an important role in the pathogenesis of atherosclerosis. Recently, two large trials in humans showed that systemic oxidative stress level is correlated with cardiovascular disease (CVD) and its various risk factors (19,34).Regular physical activity has been reported to be the most effective nonpharmacological intervention to enhance endogenous antioxidant capacity and alleviate oxidative stress-induced tissue damage (25,28,32). Several studies indicate that genetics may contribute to the systemic redox state and the susceptibility to oxidative damage, and mild to moderate genetic heritabilities of the redox state have been observed as well (21,22,41). However, none of the previous exercise intervention studies focused on a genetic association with the systemic oxidative stress level response to exercise training.The NADPH oxidase system plays a key role in generating reactive oxygen species (ROS), including superoxide and hydrogen peroxide in phagocytic cells, fibroblasts, vascular smooth muscle cells, and endothelial cells (2, 10, 29). The NADPH oxidase system is regula...

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

“…Regular physical activity has been reported to be the most effective non-pharmacological intervention to enhance endogenous antioxidant capacity and alleviate oxidative stress-induced tissue damage. 30 Our findings on the interaction between variants of the CYBA gene and physical activity were in line with the results of a recently published study 15 in which 59 apparently healthy Caucasian men and women participated in an exercise training program. Carriers of the A allele of the rs1049255 polymorphism displayed a significantly greater decrease in superoxide production after exercise training compared with the A allele noncarrier group.…”

“…First, our population-based study suggested a genetic association with arterial elasticity indices that could be modified by physical activity but did not directly measure the biochemical indices related to superoxide production to verify our hypothesis. Second, we did not perform an intervention study of physical activity that could reflect the effect of energy expenditure on polymorphisms directly; however, our results were in accordance with the previous study, 15 which used the interventional method to evaluate the physical exercise. Furthermore, our definition of physical activity was based on the data of the present study; nevertheless, the cutoff point for the division of physically active and less active participants was similar to the mean energy expenditure in Chinese residents with occupations requiring a moderate amount of physical activity (2581 kcal per day).…”

“…13,14 Therefore, in the present study, we hypothesized that the rs1049255 and rs7195830 polymorphisms of the CYBA gene are associated with arterial elasticity indices in a large cohort of apparently healthy Chinese individuals across a wide age range. As physical activity may influence oxidative stress biomarkers, 15 we further explored whether physical activity could modify the genetic effect.…”

Genetic polymorphisms of NAD(P)H oxidase: variation in subunit expression and enzyme activity

“…These results were reproducible in both study groups regardless of the applied stimulus. A functional significance of the CYBA 640A4G SNP might be supported by a recent report 25 in which carriers of the wild-type A allele responded better to exerciseinduced reduction in plasma thiobarbituric acid reactive substances, an indicator of ROS-mediated lipid oxidation. In our analyses, CYBA 640G4A was not implicated in transcript numbers of CYBA.…”

Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas

“…Opposed to the effects of both mechanisms (gene polymorphisms of eNOS and of the production of O 2 -), aerobic exercise has been indicated as a major stimulus to combat these endothelial disorders 2,19,20 . The shear stress induced by the increase in blood flow, especially during physical exercises, may benefit the cardiovascular control mechanism in almost two mechanisms.…”