Nunes Rafael Amorim Belo, Barroso Lúcia Pereira, Pereira Alexandre da Costa, Krieger José Eduardo, Mansur Alfredo José
Heart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , Brazil.
Institute of Mathematics and Statistics, Universidade de São Paulo , São Paulo , Brazil.
Open Heart. 2014 Dec 22;1(1):e000132. doi: 10.1136/openhrt-2014-000132. eCollection 2014.
Treadmill exercise test responses have been associated with cardiovascular prognosis in individuals without overt heart disease. Neurohumoral and nitric oxide responses may influence cardiovascular performance during exercise testing. Therefore, we evaluated associations between functional genetic polymorphisms of α-adrenergic receptors, endothelial nitric oxide synthase, bradykinin receptor B2 and treadmill exercise test responses in men and women without overt heart disease.
We enrolled 766 (417 women; 349 men) individuals without established heart disease from a check-up programme at the Heart Institute, University of São Paulo Medical School. Exercise capacity, chronotropic reserve, maximum heart-rate achieved, heart-rate recovery, exercise systolic blood pressure (SBP), exercise diastolic blood pressure (DBP) and SBP recovery were assessed during exercise testing. Genotypes for the α-adrenergic receptors ADRA1A Arg347Cys (rs1048101), ADRA2A 1780 C>T (rs553668), ADRA2B Del 301-303 (rs28365031), endothelial nitric synthase (eNOS) 786 T>C (rs2070744), eNOS Glu298Asp (rs1799983) and BK2R (rs5810761) polymorphisms were assessed by PCR and high-resolution melting analysis.
Maximum SBP was associated with ADRA1A rs1048101 (p=0.008) and BK2R rs5810761 (p=0.008) polymorphisms in men and ADRA2A rs553668 (p=0.008) and ADRA2B rs28365031 (p=0.022) in women. Maximum DBP pressure was associated with ADRA2A rs553668 (p=0.002) and eNOS rs1799983 (p=0.015) polymorphisms in women. Exercise capacity was associated with eNOS rs2070744 polymorphisms in women (p=0.01) and with eNOS rs1799983 in men and women (p=0.038 and p=0.024).
The findings suggest that genetic variants of α-adrenergic receptors and bradykinin B2 receptor may be involved with blood pressure responses during exercise tests. Genetic variants of endothelial nitric oxide synthase may be involved with exercise capacity and blood pressure responses during exercise tests. These responses may be gender-related.
在无明显心脏病的个体中，跑步机运动试验反应与心血管预后相关。神经体液和一氧化氮反应可能会影响运动试验期间的心血管功能。因此，我们评估了α-肾上腺素能受体、内皮型一氧化氮合酶、缓激肽受体B2的功能基因多态性与无明显心脏病的男性和女性跑步机运动试验反应之间的关联。
我们从圣保罗大学医学院心脏研究所的一项体检计划中招募了766名（417名女性；349名男性）无确诊心脏病的个体。在运动试验期间评估运动能力、变时性储备、达到的最大心率、心率恢复、运动收缩压（SBP）、运动舒张压（DBP）和SBP恢复情况。通过聚合酶链反应和高分辨率熔解分析评估α-肾上腺素能受体ADRA1A Arg347Cys（rs1048101）、ADRA2A 1780 C>T（rs553668）、ADRA2B Del 301 - 303（rs28365031）、内皮型一氧化氮合酶（eNOS）786 T>C（rs2070744）、eNOS Glu298Asp（rs1799983）和BK2R（rs5810761）多态性的基因型。
男性中最大收缩压与ADRA1A rs1048101（p = 0.008）和BK2R rs5810761（p = 0.008）多态性相关，女性中与ADRA2A rs553668（p = 0.008）和ADRA2B rs28365031（p = 0.022）相关。女性中最大舒张压与ADRA2A rs553668（p = 0.002）和eNOS rs1799983（p = 0.015）多态性相关。女性的运动能力与eNOS rs2070744多态性相关（p = 0.01），男性和女性的运动能力与eNOS rs1799983相关（p = 0.038和p = 0.024）。
研究结果表明，α-肾上腺素能受体和缓激肽B2受体的基因变异可能与运动试验期间的血压反应有关。内皮型一氧化氮合酶的基因变异可能与运动试验期间的运动能力和血压反应有关。这些反应可能与性别有关。
