Endothelial nitric oxide synthase Glu298Asp gene polymorphism is associated with hypertensive response to exercise in well-controlled hypertensive patients

Purpose: Hypertensive response to exercise (HRE) is known to be an adverse prognostic factor for future cardiovascular events and may be associated to endothelial dysfunction. Previous studies regarding endothelial nitric oxide synthase (eNOS) Glu298Asp 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. Patients and Methods: Two hundred sixty nine patients who underwent treadmill test were enrolled in this study; 77 patients (mean age 55.8 ± 9.4 years) had hypertensive response (peak systolic BP of ≥ 210 mmHg in men and ≥ 190 mmHg in women). Pulse wave velocity (PWV) was measured on 153 patients of them. The Glu298Asp exchange in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan. Results: The percentages of the GG, GT and TT genotypes were 81.0, 18.6 and 0.4%, respectively. The presence of GT or TT genotype was independently associated with prevention of HRE when controlled for age, sex, baseline systolic BP and homeostatic model assessment (HOMA) index (OR = 0.35, p = 0.016). Subgroup analysis showed that preventive effect for HRE of T allele was significant in females (p < 0.001) and patients without insulin resistance (p = 0.009). Conclusion: In our study, eNOS Glu298Asp polymorphism was significantly associated with HRE. This result suggests that the presence of T allele of the Glu298Asp polymorphism may be a favorable factor to in preventing HRE, especially in female and patients without insulin resistance.