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


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 > or = 210 mmHg in men and > or = 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).


CONCLUSIONS
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.
Kim
Jung-Sun
JS
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Cho
Jung Rae
JR
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Park
Sungha
S
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Genome Center, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
Shim
Jaemin
J
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Kim
Jin-Bae
JB
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Cho
Deok-Kyu
DK
Division of Cardiology, Cardiovascular Center, Gwandong University College of Medicine, Goyang, Korea.
Shin
Hyun-Joon
HJ
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Park
Chan Mi
CM
Cardiovascular Genome Center, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
Ko
Young-Guk
YG
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Ha
Jong-Won
JW
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Choi
Donghoon
D
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Rim
Se-Joong
SJ
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
Jang
Yangsoo
Y
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Genome Center, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
Chung
Namsik
N
Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis
D052250:Nitric Oxide Synthase Type III