Nishijima Tsunenori, Nakayama Masafumi, Yoshimura Michihiro, Abe Koji, Yamamuro Megumi, Suzuki Satoru, Shono Makoto, Sugiyama Seigo, Saito Yoshihiko, Miyamoto Yoshihiro, Nakao Kazuwa, Yasue Hirofumi, Ogawa Hisao
The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Pharmacogenet Genomics. 2007 Aug;17(8):581-7. doi: 10.1097/01.fpc.0000239978.61841.1a.
We previously found a -786T/C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene and reported that this polymorphism is strongly associated with coronary spasm. In this study, we examined whether the polymorphism is a prognostic marker in coronary spasm patients.
We examined the clinical courses of 201 consecutive patients with coronary spasm who were admitted to our institution: 146 patients with the -786T/T genotype; 50 patients with the -786C/T genotype; and five patients with the -786C/C genotype. The mean follow-up period was 76+/-60 months. All the patients took calcium channel blockers and/or nitrate during the follow-up period. In this study, no patients died due to a cardiac event. About 25 patients were readmitted owing to cardiovascular disease. Out of these 25 patients, 23 patients were readmitted owing to a reattack of coronary spasm. The -786C allele was significantly associated with readmission due to coronary spasm (P=0.0072, odds ratio: 3.37 in the dominant effect). Kaplan-Meier analysis revealed that the occurrence of readmission was significantly higher in the patients with the -786C allele than in the patients without the -786C allele (P=0.0079). Further, multiple logistic regression analysis revealed that the -786T/C polymorphism was an independent predictor for readmission due to reattack of coronary spasm (P=0.006; relative risk=3.590).
The eNOS -786C allele is an independent risk factor for readmission due to a recurrent attack of coronary spasm in patients with coronary spasm, even if the patients have taken calcium channel blockers and/or nitrate.
我们之前在内皮型一氧化氮合酶（eNOS）基因的5'侧翼区域发现了一个-786T/C多态性，并报道该多态性与冠状动脉痉挛密切相关。在本研究中，我们检测了该多态性是否为冠状动脉痉挛患者的预后标志物。
我们检查了连续入住我院的201例冠状动脉痉挛患者的临床病程：146例为-786T/T基因型患者；50例为-786C/T基因型患者；5例为-786C/C基因型患者。平均随访期为76±60个月。所有患者在随访期间均服用钙通道阻滞剂和/或硝酸盐。在本研究中，无患者因心脏事件死亡。约25例患者因心血管疾病再次入院。在这25例患者中，23例因冠状动脉痉挛复发再次入院。-786C等位基因与因冠状动脉痉挛再次入院显著相关（P = 0.0072，优势比：显性效应下为3.37）。Kaplan-Meier分析显示，具有-786C等位基因的患者再次入院的发生率显著高于无-786C等位基因的患者（P = 0.0079）。此外，多因素逻辑回归分析显示，-786T/C多态性是冠状动脉痉挛复发导致再次入院的独立预测因子（P = 0.006；相对风险 = 3.590）。
即使患者服用了钙通道阻滞剂和/或硝酸盐，eNOS -786C等位基因仍是冠状动脉痉挛患者因冠状动脉痉挛复发而再次入院的独立危险因素。
