Evidence for association between endothelial nitric oxide synthase gene polymorphism (G894T) and inflammatory markers: the ATTICA study.
BACKGROUND
We evaluated the effect of the point mutation of guanine to thymine at nucleotide position 894 (G894T) of the endothelial nitric oxide synthase (eNOS) gene on inflammatory and oxidative stress markers.


METHODS
We studied genetic information from 270 men (18-87 years old) and 325 women (18-89 years old). Participants without any clinical evidence of cardiovascular or other atherosclerotic disease were randomly selected from the general population according to the age-sex distribution of Athens greater area. Genomic DNA was extracted from 2 to 5 mL of fresh or frozen whole blood using standard methods.


RESULTS
The DNA analysis showed that 10.6% of the participants were Asp-homozygotes (Asp/Asp), 40% heterozygotes (Asp/Glu) and 49.4% Glu-homozygotes (Glu/Glu). Compared to Asp/Glu and Glu/Glu, Asp/Asp had higher levels of fibrinogen (332 +/- 46 or 329 +/- 33 vs 319 +/- 29 mg/dL, P =.029), white blood cells (6.9 +/- 0.6 or 6.5 +/- 0.3 vs 6.1 +/- 0.9 x 10(3) counts, P =.044), and oxidized low-density lipoprotein cholesterol (68 +/- 21 or 61 +/- 22 vs 59 +/- 20 mg/dL, P =.039), after controlling for several potential confounders. An insignificant association was found between homocysteine (P =.08), C-reactive protein (P =.096), and the distribution of G894T polymorphism (P <.1). No association between the distribution of the polymorphism and hypertension status of the participants was observed.


CONCLUSIONS
Our results imply that G894T polymorphism of the endothelial nitric oxide synthase gene is associated with elevated levels of inflammatory and oxidative stress markers, which may partially explain the increased prevalence of G894T polymorphism among patients with cardiovascular disease.
First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece.
Christine
C
Chrysohoou
Demosthenes B
DB
Panagiotakos
Christos
C
Pitsavos
Charalambos
C
Antoniades
John
J
Skoumas
Michael
M
Brown
Christodoulos
C
Stefanadis
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D017354:Point Mutation; D011110:Polymorphism, Genetic; D000685:Serum Amyloid A Protein / Q000032:analysis
D015415:Biomarkers; D008078:Cholesterol, LDL; D000685:Serum Amyloid A Protein; D006710:Homocysteine; D005340:Fibrinogen; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III