title: The endothelial nitric oxide synthase T-786c mutation, a treatable etiology of Prinzmetal's angina.
abstract: We assessed to what degree the endothelial nitric oxide synthase (eNOS) T-786C polymorphism, leading to reduced nitric oxide (NO) production-coronary artery spasm, was reversibly associated with Prinzmetal's variant angina (PVA). ENOS T-786C PCR analyses were done in 19 women, 8 men, 26 Caucasian, 1 African-American, median age 53, with well-documented PVA and in 72 healthy controls who did not differ by race or gender. Of the 27 cases, 7 (26%) were homozygous for wild-type normal eNOS (CC), 13 (48%) were T-786C heterozygotes (CT), and 7 (26%) were T-786C homozygotes (TT) vs controls, 44 (61%) CC, 27 (38%) TC, and 1 (1%) TT, P < 0.0001. The mutant eNOS T-786C allele frequency in PVA patients was 27/54 (50%) vs 29/144 (20%) in controls, P < 0.0001. On oral L-arginine (9.2 g/d) to increase production of NO for a median of 4.7 months in 16 PVA patients with symptomatic angina despite conventional nitrate-calcium channel blockers, using the Seattle Angina Questionnaire, satisfaction with symptom remission rose (median) from 50% to 100% (P = 0.004), satisfaction with angina frequency reduction rose from 65% to 80% (P = 0.02), satisfaction with treatment for symptoms rose from 38% to 88% (P = 0.001), and perception of overall life status rose from 25 to 71% (P = 0.0002). On L-arginine (median 4.7 months), in 20 patients, none had worsening of angina, and of 7 patients whose angina totally resolved, eNOS T-786C homozygosity was over-represented, P = 0 .04. The eNOS T-786C mutation appears to be a reversible etiology of PVA in patients whose angina may be ameliorated by L-arginine.
authors.affiliation: Cholesterol and Metabolism Center, Department of Internal Medicine, Jewish Hospital of Cincinnati, Cincinnati, OH 45229, USA. cjglueck@health-partners.org
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Alejandro
authors.initials: A
authors.lastname: Valdes
authors.forename: Dedrick
authors.initials: D
authors.lastname: Bowe
authors.forename: Siddharth
authors.initials: S
authors.lastname: Munsif
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000788:Angina Pectoris, Variant / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D001120:Arginine / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009566:Nitrates / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D002121:Calcium Channel Blockers; D009566:Nitrates; D001120:Arginine; D052250:Nitric Oxide Synthase Type III