The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels.
OBJECTIVE
Genetic variants of the endothelial nitric oxide synthase (eNOS) gene, Glu298Asp and T-786C, have been reported to be associated with cardiovascular disease. Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and vascular protective effects; its levels are typically low in metabolic syndrome. Therefore, eNOS gene polymorphisms may also be associated with specific metabolic profiles, including plasma adiponectin levels and atherogenic lipids.


METHODS
We evaluated the functional significance of eNOS gene Glu298Asp and T-786C polymorphisms on endothelial function and metabolic profiles in 101 healthy young men (mean age 30.3 years) before the progression of atherosclerotic lesions.


RESULTS
No linkage disequilibrium was found between the two genotypes. The Asp298 allele carriers of the eNOS gene presented significantly higher plasma low density lipoprotein (LDL) cholesterol, LDL particle size, malondialdehyde-modified LDL (MDA-LDL), and fasting insulin levels and lower plasma high density lipoprotein (HDL) cholesterol, apolipoprotein A-I levels, and endothelium-dependent vasodilation when compared with noncarriers. In spite of higher MDA-LDL levels, Asp298 carriers had significantly larger LDL particle size. By contrast, in C-786 allele carriers, systolic blood pressure was significantly higher, and plasma high-molecular-weight adiponectin levels and endothelium-dependent vasodilation were significantly lower than those in non-carriers.


CONCLUSIONS
Although both eNOS polymorphisms induced endothelial dysfunction, the eNOS T-786C polymorphism may be associated with adiponectin levels, whereas the Glu298Asp polymorphism may be associated with atherogenic lipid levels.
Imamura
Akiko
A
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takahashi
Ryotaro
R
Murakami
Ryuichiro
R
Kataoka
Hiroki
H
Cheng
Xian Wu
XW
Numaguchi
Yasushi
Y
Murohara
Toyoaki
T
Okumura
Kenji
K
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001224:Aspartic Acid; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005973:Glutamine; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D012016:Reference Values; D012039:Regional Blood Flow; D012307:Risk Factors; D014664:Vasodilation
D052242:Adiponectin; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005973:Glutamine; D001224:Aspartic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III