Cholesterol and Metabolism Center, Department of Internal Medicine, Jewish Hospital of Cincinnati, Cincinnati, OH 45229, USA.
Transl Res. 2013 Jul;162(1):64-6. doi: 10.1016/j.trsl.2013.03.003. Epub 2013 Apr 6.
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.
我们评估了内皮型一氧化氮合酶（eNOS）T-786C 多态性（导致一氧化氮（NO）产生减少-冠状动脉痉挛）与变异型心绞痛（PVA）之间的可逆关联程度。对 19 名女性、8 名男性、26 名高加索人、1 名非裔美国人（中位年龄 53 岁）进行了 eNOS T-786C PCR 分析，这些人患有经证实的 PVA，且与种族或性别无关，72 名健康对照组也进行了分析。在 27 例病例中，7 例（26%）为正常 eNOS（CC）纯合野生型，13 例（48%）为 T-786C 杂合型（CT），7 例（26%）为 T-786C 纯合型（TT），与对照组相比，44 例（61%）为 CC，27 例（38%）为 TC，1 例（1%）为 TT，P<0.0001。PVA 患者的突变 eNOS T-786C 等位基因频率为 27/54（50%），对照组为 29/144（20%），P<0.0001。在 16 例有症状心绞痛的 PVA 患者中，使用西雅图心绞痛问卷，中位时间为 4.7 个月，给予口服 L-精氨酸（9.2 g/d）以增加 NO 的产生，对 L-精氨酸的治疗满意度（中位数）从 50%升高至 100%（P=0.004），对心绞痛发作频率减少的满意度从 65%升高至 80%（P=0.02），对治疗症状的满意度从 38%升高至 88%（P=0.001），对整体生活状况的感知从 25%升高至 71%（P=0.0002）。在 L-精氨酸（中位数 4.7 个月）治疗期间，20 例患者的心绞痛均未恶化，且 7 例心绞痛完全缓解的患者中，eNOS T-786C 纯合子的比例过高，P=0.04。eNOS T-786C 突变似乎是 PVA 患者的一种可逆病因，其心绞痛可能通过 L-精氨酸得到改善。
