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| Endothelial nitric oxide synthase Glu298Asp gene polymorphism is associated with hypertensive response to exercise in well-controlled hypertensive patients |
| ¹Division of Cardiology,²Cardiovascular Research Institute and Genome Center, Yonsei Cardiovascular Hospital,Yonsei University College of Medicine,³Division of Genetic Disease, Department of Biomedical Sciences,National Institute of Health,Seoul,Korea |
| Jung-Sun Kim¹, Sungha Park¹, Chanmi Park², Young-Guk Ko¹, Donghoon Choi¹, Hyun-Young Park³, Yangsoo Jang¹, Namsik Chung¹ |
Background Hypertensive response to exercise (HRE) is known to be an adverse prognostic factor for cardiovascular events in the future. Endothelial dysfunction during exercise may be important in the pathogenesis of hypertensive response to exercise. Previous studies done regarding endothelial nitric oxide synthase (e-NOS) Glu298Asp (E/D) gene polymorphism focused upon its relation to hypertension. In this study, we hypothesize that the polymorphism may be associated with inherent difference in endothelial response to exercise. Therefore we investigated the association of e-NOS Glu298Asp gene polymorphism with HRE.
Method Two hundred seventy patients with well-controlled, essential hypertension (BP < 160/100mmHg) who underwent treadmil test were enrolled in this study; 77 patients (mean age 55.8±9.4 years) had hypertensive response, defined as peak systolic BP of ≥210mmHg in men and ≥190mmHg in women and 193 patients (mean age: 53.9±8.8 years) had absence of hypertensive response. The e-NOS E298D exchange (G894T) in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan.
Result The percentages of the EE298 (GG), ED298 (GT) and DD298 (TT) genotypes were 81.1, 18.5, 0.4 %, respectively. The presence of GT or TT genotype, assuming co-dominant effect of the T allele, was independently associated with prevention of hypertensive response when controlled for age, sex, baseline systolic blood pressure and HOMA index [OR=0.35(0.14-0.82), P-value = 0.016]. Subgroup analysis showed that this effect was significant in females but not in males, with female patients with GT or TT genotype demonstrating absence of hypertensive response with significantly lower increment of systolic blood pressure response during exercise compared to the GG genotype (48.8±23.3 vs. 34.4±13.0, p < 0.001).
Conclusion In our study, e-NOS E298D gene polymorphism was significantly associated with hypertensive response to exercise in well-controlled hypertension. This result suggests that the presence of T allele of the E298D polymorphism may be a favorable factor to in preventing HRE, especially in female patients.
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