Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism is Associated with Hypertensive Response to Exercise in Well-Controlled Hypertensive Patients
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Abstract
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 ≥210mmHg in men and ≥190mmHg 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.
참고문헌 (29)
- Filipovsky J, "Prognostic significance of exercise blood pressure and heart rate in middle-aged men", 20, pp.333~9 (1992)
- Mundal R, "Exercise blood pressure predicts cardiovascular mortality in middle-aged men", 24, pp.56~62 (1994)
- Mottram PM, "Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy", 43, pp.848~853 (2004)
- Wilson MF, "Exaggerated pressure response to exercise in men at risk for systemic hypertension", 66, pp.731~6 (1990)
- Andersen UB, "Exercise blood pressure is related to insulin resistance in subjects with two hypertensive parents", 12, pp.314~318 (2003)
- Isaksson H, "Therapy-resistant hypertension associated with central obesity,insulin resistance,and large muscle fiber area", 2, pp.46~52 (1993), Blood Press
- Reaven GM, "Hypertension and associated metabolic abnormalities-the role of insulin resistance and the sympathoadrenal system", 334, pp.374~381 (1996)
- Julius K, "The interconnection between sympathetics,microcirculation,and insulin resistance in hypertension", 1, pp.9~19 (1992), Blood Press
- Hirose H, "Insulin resistance and hypertension:seven-year follow-up study in middle-aged Japanese men(the KEIO study)", 23, pp.795~800 (2003)
- Ciuffetti G, "Capillary rarefaction and abnormal cardiovascular reactivity in hypertension", 21, pp.2297~2303 (2003)
- Pierson LM, "Relationship between exercise systolic blood pressure and left ventricular geometry in overweight,mildly hypertensive patients", 22, pp.399~405 (2004)
- Gilligan DM, "Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation", 90, pp.2853~8 (1994)
- Tanus-Santos JE, "Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants", 11, pp.719~725 (2001)
- Tesauro M, "Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298", 97, pp.2832~2835 (2000)
- Park S, "Insulin resistance is associated with hypertensive response to exercise in non-diabetic hypertensive patients", 73, pp.65~69 (2006)
- Fairchild TA, "Acidic hydrolysis as a mechanism for the cleavage of the Glu298Asp variant of human endothelial nitric-oxide synthase", 276, pp.26674~26679 (2001)
- Miyamoto Y, "Endothelial nitric oxide synthase gene is positively associated with essential hypertension", 32, pp.3~8 (1998)
- Karvonen J, "Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure,left ventricular mass and carotid artery atherosclerosis in a population-based cohort", 251, pp.102~110 (2002)
- Chrysohoou C, "Evidence for association between endothelial nitric oxide synthase gene polymorphism (G894T) and inflammatory markers: the ATTICA study", 148, pp.733~738 (2004)
- Tsujita Y, "Association analyses between genetic polymorphisms of endothelial nitric oxide synthase gene and hypertension in Japanese:The Suita Study", 19, pp.1941~1948 (2001)
- Sandrim VC, "Susceptible and protective eNOS haplotypes in hypertensive black and white subjects", 186, pp.428~432 (2006)
- Sandrim VC, "Endothelial nitric oxide synthase haplotypes affect the susceptibility to hypertension in patients with type 2 diabetes mellitus", 189, pp.241~246 (2006)
- Malhotra S, "Effects of NOS3 Glu298Asp polymorphism on hemodynamic reactivity to stress:influences of ethnicity and obesity", 44, pp.866~871 (2004)
- Szolnoki Z, "Endothelial nitric oxide synthase gene interactions and the risk of ischaemic stroke", 111, pp.29~33 (2005)
- Szolnoki Z, "Coexistence of angiotensin II Type-1 receptor A1166C and angiotensin-converting enzyme D", D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke, 2006, pp.8, 353~360
- Szolnoki Z, "Gene-gene and gene-environment interplay represent specific susceptibility for different types of ischaemic stroke and leukoaraiosis", 13, pp.1627~1634 (2006)
- Hsueh WA, "Insulin resistance and the endothelium", 117, pp.109~117 (2004)
- Khalil RA, "Sex hormones as potential modulators of vascular function in hypertension", 46, pp.249~254 (2005)
- Stauffer BL, "Gender differences in endothelial tissue- type plasminogen activator release in middle-age adults", 45, pp.1547~1548 (2005)