The endothelial nitric oxide synthase T-786c mutation, a treatable etiology of Prinzmetal's angina

Glueck, Charles J.; Valdés, Alejandro Roque; Bowe, Dedrick; Munsif, Siddharth; Wang, Ping

doi:10.1016/j.trsl.2013.03.003

Cited by 18 publications

(27 citation statements)

References 4 publications

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“…The current 59 PVA cases did not differ from our previously reported 27 PVA cases [11] by the eNOS genotype, 12 (20%) TT, 32 (54%) TC in 59 cases vs. 7 (26%) TT, 13 (48%) TC in the 27 cases (p = .8), and did not differ by the percentage of patients with mutant alleles, 47% vs. 50% (p = .8). The current 59 cases did differ from our previously published 43 cases [10] in regards to the eNOS genotype: 12 (20%) TT, 32 (54%) TC in the current 59 cases vs. 3 (7%) TT, 19 (44%) TC in 43 cases, p = .007, and also differed by having more mutant alleles, 47% vs. 29%, p = .008.…”

Section: Resultscontrasting

confidence: 66%

“…Fifty-nine not previously reported [10,11] patients with PVA and intractable angina despite conventional calcium channel blockernitrate therapy were studied in the sequence of their referral by their cardiologists and physicians. The diagnosis of PVA was confirmed by transient ST elevation during angina attacks at rest in patients with normal coronary angiography, or by ergonovine or acetylcholine-induced coronary vasospasm during coronary angiography.…”

Section: Casementioning

confidence: 99%

“…Patients were asked to fill out the SAQ [34] at their first pretreatment assessment, and after 1 month and then every 3 months on 9.0 g/day oral L-arginine (Arginaid), [10,11]. Patients were instructed to retain their usual anti-angina therapy with long acting nitrates and calcium channel blockers unchanged during the study period to allow assessment of changes in angina on treatment with L-arginine.…”

Section: Casementioning

confidence: 99%

“…Deficient release of nitric oxide (NO) is an important factor in the pathogenesis of CAS [8] in PVA [4,[9][10][11]. A thymine replacement by cytosine at nucleotide -786 of the endothelial NO synthase (eNOS) gene reduces eNOS gene promoter activity and reduces levels of the potent coronary artery vasodilator, NO [12].…”

Section: Introductionmentioning

confidence: 99%

“…In our second study of PVA [11], we evaluated 27 patients with welldocumented PVA, compared to 72 healthy controls who did not differ by race or gender. Of the 27 cases, 7 (26%) were homozygous for wildtype normal eNOS (CC), 13 (48%) were T-786C heterozygotes (TC), and 7 (26%) were T-786C homozygotes (TT) vs. controls, 44 (61%) CC, 27 (38%) TC, and 1 (1%) TT, p b 0.0001.…”

Section: Introductionmentioning

confidence: 99%

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The eNOS T786C mutation, Prinzmetal's Variant Angina, and amelioration of angina by l-arginine in 59 patients with intractable angina despite calcium channel blocker–nitrate therapy

Glueck

Prince

Shah

et al. 2015

IJC Metabolic & Endocrine

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a b s t r a c tBackground: Despite calcium channel blockers -long acting nitrates (CaCH-LAN),~20% of patients with Prinzmetal's Variant Angina (PVA) retain intractable angina. The endothelial nitric oxide synthase (eNOS) T-786C polymorphism, more common in PVA than normal subjects, decreases the conversion of L-arginine to nitric oxide (NO), promoting coronary artery spasm (CAS)-angina. Methods: PCR measures for the eNOS T-786C polymorphism were done in 59 PVA patients with intractable angina despite CaCH-LAN. Using the Seattle Angina Questionnaire (SAQ), effects of 9 g L-arginine/day were prospectively assessed in 28 patients with ≥3 visits, pre-treatment entry and ≥2 follow-ups at 1 and 5 months, and in 31 additional patients with 2 visits, entry and 7.7 months on L-arginine. This allowed an assessment of response to L-arginine in 59 patients at entry and 12 months later (last follow-up). Results: In the cohort of 59 patients, 47% of eNOS alleles were mutant vs. 20% in 72 normal controls, p b .0001. Compared to pre-treatment baseline, all 5 SAQ components improved in 28 patients at 1 (p ≤ .02 for all) and 5 months (p ≤ .03 for all) on L-arginine treatment, and improved in the 59 patients after 12 months on L-arginine, p ≤ .002 for all. The eNOS mutation was a significant positive independent determinant of reduction in anginal symptoms, p = .0002. Patients hetero-and homozygous for the eNOS mutation had greater improvement in anginal symptoms. Conclusions: In patients with intractable angina despite CaCH-LAN, the eNOS T-786C mutation appears to facilitate CAS via reduced NO production, a condition susceptible to treatment with L-arginine.

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Section: Resultscontrasting

confidence: 66%

Section: Casementioning

confidence: 99%