Cardiovascular Center, Taichung Veterans General Hospital, 1650 Taiwan Boulevard, Sec. 4, Taichung, 40705, Taiwan.
Department of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan.
Heart Vessels. 2021 May;36(5):615-620. doi: 10.1007/s00380-020-01733-7. Epub 2021 Jan 3.
Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT) repeat of the HO-1 gene (HMOX1) promoter has a lower transcription rate. Subjects with longer GT repeats in the HMOX1 promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) < 50% from our catheterization data (N = 670). Polymerase chain reactions were performed for amplifying the HMOX1 promoter GT repeating segment to determine the number of repeats. Two subgroups, reduced EF < 40% (N = 256), and mid-range EF 40-49% (N = 414), were compared. The distribution of genotypes of SS, SL and LL were significantly different in reduced EF (29%, 48%, 23%) vs. mid-range EF CAD (64%, 30%, 5%) (S allele: ≤ 30 repeats, L allele: > 30 repeats) (p < 0.001). The patients with reduced EF had a significantly longer average (GT) (median 27.5 vs. 26.5, p = 0.004) than those with the mid-range EF. In multivariate analysis, the carrier of L allele (odds ratio 4.437, p < 0.001) was a significant predictor for the diagnosis of reduced vs. mid-range EF CAD. In conclusion, CAD patients with reduced EF had longer HMOX1 promoter (GT) repeats than those with mid-range EF.
血红素加氧酶-1（HO-1）是降解血红素为一氧化碳的限速酶。HO-1 基因（HMOX1）启动子的 GT 重复更长，转录率更低。HMOX1 启动子中 GT 重复较长的受试者更有可能患有冠状动脉疾病（CAD）和心血管事件。我们从导管插入术数据中回顾性地招募了 EF<50%的 CAD 患者（N=670）。进行聚合酶链反应以扩增 HMOX1 启动子 GT 重复片段，以确定重复次数。将 EF<40%（N=256）和中范围 EF 40-49%（N=414）的两个亚组进行比较。在 EF 降低的亚组（29%、48%、23%）与中范围 EF CAD（64%、30%、5%）中，SS、SL 和 LL 基因型的分布明显不同（S 等位基因：≤30 次重复，L 等位基因：>30 次重复）（p<0.001）。EF 降低的患者的平均（GT）（中位数 27.5 比 26.5，p=0.004）明显长于中范围 EF 的患者。在多变量分析中，L 等位基因的携带者（比值比 4.437，p<0.001）是 EF 降低与中范围 EF CAD 诊断的显著预测因子。总之，EF 降低的 CAD 患者的 HMOX1 启动子（GT）重复比中范围 EF 的患者更长。
