Endothelial nitric oxide synthase T-786C mutation, a reversible etiology of Prinzmetal's angina pectoris.
Because the endothelial nitric oxide synthase (eNOS) T-786C polymorphism is associated with reduced nitric oxide production and coronary artery spasm in Japanese patients, we speculated that it might be reversibly associated with Prinzmetal's variant angina in white Americans. Polymerase chain reaction analyses of eNOS T-786C and stromelysin 5A6A polymorphisms were done in 31 women and 12 men (42 white and 1 black American, median age 50 years), with well-documented Prinzmetal's variant angina. We matched each case with 1 healthy control by race and gender. Of the 43 cases, 21 (49%) were homozygous for wild-type normal eNOS, 19 (44%) were T-786C heterozygotes, and 3 (7%) were T-786C homozygotes. Of the 43 controls, 31 (72%) were homozygous for wild-type normal eNOS, 12 (28%) were T-786C heterozygotes, and 0 (0%) were T-786C homozygotes (p = .013). The mutant eNOS T-786C allele frequency in patients was 25 (29%) of 86 vs 12 (14%) of 86 in the controls (p = 0.016). Patients did not differ from controls for the distribution of the stromelysin 6A mutation (p = 0.66) or for the mutant 6A allele frequency (53% in cases, 50% in controls; p = 0.65). Nineteen patients took nitric oxide-elevating l-arginine (9.2 g/day, orally). Of these 19 patients, 10 (53%) became free of angina, 3 (16%) were improved but not angina free, and 6 (32%) had no change in their angina. Using l-arginine, the physical ability score (Seattle Angina Questionnaire) increased from a median of 42 to 72 of a total possible score of 100 (p = 0.011), satisfaction with symptom reduction increased from 53 to 61 (p = 0.004), and the perception of quality of life as acceptable increased from 29 to 50 (p = 0.001). In conclusion, the eNOS T-786C mutation appears to be a reversible etiology of Prinzmetal's variant angina in white Americans whose angina might be ameliorated by l-arginine.
Glueck
Charles J
CJ
Cholesterol Center, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA. glueckch@healthall.com
Munjal
Jitender
J
Khan
Ayub
A
Umar
Muhammad
M
Wang
Ping
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000788:Angina Pectoris, Variant / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D019278:Matrix Metalloproteinase 3