Shorter GT repeats in the heme oxygenase-1 gene promoter are associated with a lower severity score in coronary artery disease

Background: The glutathione thymidine repeats [(GT)n] of the heme oxygenase (HO)-1 gene promoter have been shown to be correlated with the incidence of coronary artery disease (CAD), patients with shorter repeats being less likely to have CAD. In this study, we investigated whether (GT)n repeats in the HO-1 promoter were related to a quantitative angiographic severity of CAD.

Methods: The allele frequency of the HO-1 gene promoter (GT)n repeats was examined in CAD patients with de novo lesions (n = 328). Patients' baseline coronary severity was quantified using the Jeopardy scoring system.

Results: The allele frequency of GT repeats in the HO-1 gene promoter had bimodal peaks at (GT)23 and (GT)30. Therefore, we defined allele classes as follows: S allele (<23 repeats), M allele (23-29 repeats), and L allele (≥ 30 repeats). The group with severe CAD (Jeopardy score ≥ 8) had a significantly lower frequency of the S allele (3.7% vs. 8.9%; p = 0.042) than the group with moderate CAD (Jeopardy score <8). None of the patient with the highest score of 12 (n = 17) carried the class S allele. In a multivariate binary logistic analysis, being a carrier of shorter GT repeats was a significant negative predictor (odds ratio 0.393; p = 0.024) of a higher Jeopardy score grade of CAD.

Conclusion: Our study showed that shorter (GT)n repeat in the HO-1 gene promoter were associated with a lower Jeopardy severity score in patients with significant CAD.