Subjects with coronary artery disease and reduced ejection fraction have longer (GT)n repeats in the heme-oxygenase 1 gene promoter.

Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT)n 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)n (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)n repeats than those with mid-range EF.