• Potential conflict of interest: Nothing to report.

We read with interest the results of the study of Lemaire et al., who investigated the association between the heme oxygenase-1 (HO-1) promoter (GT)n repeat variant and the presence and severity of alcoholic liver disease (ALD). Biological studies have demonstrated differences in transcriptional activity of the HO-1 promoter with different (GT)n repeat lengths, with short (GT)n repeat variants exhibiting increased HO-1 promoter activity and long (GT)n repeat variant showing reduced HO-1 inducibility.[1] Clinical studies have further suggested that the presence of the short (GT)n repeat variant is associated with a reduced risk of cardiovascular or pulmonary disease, among others, whereas conversely, there is an increased risk in patients with the long (GT)n repeat variant. Interestingly, we previously reported that HO-1 is antifibrogenic[2, 3] and that induction of HO-1 protects against alcohol-induced liver injury.[4] These data raised the interesting hypothesis that the long (GT)n repeat variant in HO-1 promoter could be associated with the presence and severity of ALD.

In their cohort study of 487 ALD Caucasian patients with cirrhosis or ALD, Lemaire et al. show that long (GT)n repeat variant polymorphism in the promoter of the HO-1 gene is not associated with the presence and the severity of ALD. However, it should be emphasized that experimental models of ALD, in which HO-1 induction is observed, only recapitulate the mild form of injury (i.e., steatosis with mild inflammation and no fibrosis). Because there is a high variability in the susceptibility of individuals to alcohol-induced liver injury, further studies should be conducted in order to evaluate whether patients with a mild form of ALD are characterized by a short (GT)n repeat variant polymorphism in the promoter of the HO-1 gene.

  • Fatima Teixeira-Clerc, Ph.D.

  • Sophie Lotersztajn, Ph.D.


  • Creteil, France