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α2A-肾上腺素能受体和内皮型一氧化氮合酶基因多态性与明显健康个体的运动肌肉血管舒张有关。

Alpha2A-adrenergic receptor and eNOS genetic polymorphisms are associated with exercise muscle vasodilatation in apparently healthy individuals.

作者信息

Amorim Belo Nunes Rafael, Pereira Barroso Lucia, da Costa Pereira Alexandre, Pinto Brandão Rondon Maria Urbana, Negrão Carlos Eduardo, Krieger José Eduardo, Mansur Alfredo José

机构信息

Unidade Clínica de Ambulatório Geral, Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, Brazil.

出版信息

Int J Cardiol Heart Vasc. 2016 Oct 13;13:14-18. doi: 10.1016/j.ijcha.2016.10.001. eCollection 2016 Dec.

Abstract

PURPOSE

Muscle vasodilatation during exercise has been associated with cardiovascular health and may be influenced by genetic variability. The purpose of this study was to evaluate functional genetic polymorphisms of physiologic pathways related to the regulation of the cardiovascular function (alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B receptor) and exercise muscle vasodilatation in apparently healthy men and women.

METHODS

We enrolled 689 individuals without established cardiovascular disease that had attended a check-up program. The vasodilatation was studied with venous occlusion plethysmography and determined by the increase of vascular conductance during handgrip exercise. Genotypes for ADRA1A Arg347Cys (rs1048101), ADRA2A 1780 C > T (rs553668), ADRA2B Del 301-303 (rs28365031), eNOS 786 T > C (rs2070744), eNOS Glu298Asp (rs1799983) and BDKRB (rs5810761) polymorphisms were assessed by polymerase chain reaction followed by high resolution melting analysis.

RESULTS

The eNOS rs2070744 polymorphism was significantly associated with forearm vascular conductance during exercise in women. Women with CC genotype showed higher vasodilatation than carriers of TC and TT genotypes (p = 0.043). The ADRA2A rs553668 polymorphism was significantly associated with forearm vascular conductance during exercise in men. Men with TT genotype had higher vasodilatation than carriers of CT and CC genotypes (p = 0.025).

CONCLUSIONS

eNOS rs207074 polymorphism in women and ADRA2A rs553668 polymorphism in men were associated with the increase of forearm vascular conductance during handgrip exercise. These findings suggest that eNOS and ADRA2A genetic polymorphisms may be potential markers of exercise muscle vasodilatation.

摘要

目的

运动期间肌肉血管舒张与心血管健康相关,且可能受基因变异性影响。本研究的目的是评估与心血管功能调节(α-肾上腺素能受体、内皮型一氧化氮合酶和缓激肽B受体)及运动肌肉血管舒张相关的生理途径的功能性基因多态性,研究对象为表面健康的男性和女性。

方法

我们纳入了689名未患心血管疾病且参加过体检项目的个体。采用静脉阻塞体积描记法研究血管舒张情况,并通过握力运动期间血管传导率的增加来确定。通过聚合酶链反应随后进行高分辨率熔解分析,评估ADRA1A Arg347Cys(rs1048101)、ADRA2A 1780 C>T(rs553668)、ADRA2B Del 301-303(rs28365031)、eNOS 786 T>C(rs2070744)、eNOS Glu298Asp(rs1799983)和BDKRB(rs5810761)基因多态性。

结果

eNOS rs2070744基因多态性与女性运动期间的前臂血管传导率显著相关。CC基因型女性的血管舒张程度高于TC和TT基因型携带者(p = 0.043)。ADRA2A rs553668基因多态性与男性运动期间的前臂血管传导率显著相关。TT基因型男性的血管舒张程度高于CT和CC基因型携带者(p = 0.025)。

结论

女性中的eNOS rs207074基因多态性和男性中的ADRA2A rs553668基因多态性与握力运动期间前臂血管传导率的增加相关。这些发现表明,eNOS和ADRA2A基因多态性可能是运动肌肉血管舒张的潜在标志物。

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