Genetic evaluation of the common variant of the endothelial nitric oxide synthase (Glu(298)-><Asp) in patients with thromboangiitis obliterans.
BACKGROUND
Nitric oxide is synthesized by endothelial nitric oxide synthase and plays a key role in adequate endothelial function. An important effect is the reduction of free radicals caused by cigarette smoking, which is the only established risk factor for thromboangiitis obliterans (TAO). In patients with TAO a genetic defect of endothelial nitric oxide synthase may therefore result in deteriorated endothelial function. The aim of our study was to evaluate whether a genetic defect of the common variant of endothelial nitric oxide synthase (Glu(298)-->Asp) can be found in a higher degree in patients with TAO compared to healthy controls.


METHODS
We enrolled 42 patients with TAO and 149 healthy subjects.


RESULTS
Nineteen patients (45.2%) showed homozygosity for Glu(298) versus 76 (51%) in the control group. The heterozygous status for Glu(298)-->Asp was found among 18 patients (42.9%) compared to 61 (40.9%) members of the control group, which was a nearly equal distribution. Homozygosity for the mutant Asp(298) was slightly elevated in the patient group with 11.9 versus 8.1% in the control group. Allele frequency for Asp(298) was 0.333.


CONCLUSIONS
Our data do not show elevated homozygosity for the common variant Glu(298)-->Asp in patients with TAO compared to healthy controls. The limitation of our evaluation is the small number of patients, which is a general problem when evaluating patients with TAO, as this is not a common disease.
Division of Angiology, Department of Internal Medicine, Karl-Franzens University Graz, Graz, Austria. marianne.broadmann@kfunigraz.ac.at
M
M
Brodmann
W
W
Renner
G
G
Seinost
E
E
Pabst
G
G
Stark
E
E
Pilger
D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D014644:Genetic Variation; D018698:Glutamic Acid / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D012907:Smoking; D013919:Thromboangiitis Obliterans / Q000201:enzymology*
D001224:Aspartic Acid; D018698:Glutamic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III