A microsatellite polymorphism in the Heme Oxygenase – 1 gene promoter is associated with increased serum bilirubin and HDl levels but not with a decreased risk for coronary artery disease

Abstract number: P0474

Endler G., Exner M., Schillinger M., Marculescu R., Sunder-Plassmann R., Raith M., Huber K., Mannhalter CH., Wagner O.

University of Vienna, Austria

Background  

Heme oxygenase 1 (HO-1) catalyses the conversion of heme to the endogenous antioxidant bilirubin, which has been suggested to exert beneficial effects against atherosclerotic vascular disease. Recently, a (GT) repeat polymorphism in the HO-1 promoter region has been reported to modulate HO-1 expression in response to oxidative stress. Short (<25) GT repeats were associated with HO-1 up-regulation, and thus this genotype may reduce the risk for atherosclerosis. Indeed, this polymorphism has been reported to protect from coronary artery disease in Orientals. In our study, we intended to confirm this observation in Caucasians, and investigate potential underlying influences of the HO-1 genotype on cardiovascular risk factors.

Patient and methods  

We studied 649 consecutive individuals with myocardial infarction (n = 258), stable coronary artery disease (n = 180) and without coronary artery disease (n = 211). The association between the HO-1 genotype and cardiovascular risk factors was studied and the HO-1 allele frequencies were compared between the three patient groups adjusting for potentially confounding factors.

Results and discussion  

Carriers of short (S) alleles (<25 repeats) had higher serum bilirubin levels (median 0.66 mg dL^-1, IQR 0.49–0.91) compared to S allele noncarriers (median 0.61 mg dL^-1, IQR 0.45–0.82; P = 0.03) and had a more favorable lipid profile (HDL median 47 mg dL^-1, IQR 40–50 vs. median 45, IQR 37–55, P = 0.01; triglycerides median 118 mg dL^-1, IQR 87–174 vs. median 132, IQR 97–191, P = 0.03). No significant differences of the genotype distribution were observed between the three study groups in this Caucasian population (P = 0.94).

Conclusion  

In contrast to Orientals, the HO-1 genotype was not significantly associated with coronary artery disease in Caucasians. Although potentially beneficial effects of the short HO-1 allele on lipid profile and serum bilirubin were observed, these effects may be too small to protect from the development of coronary artery disease in Caucasians.