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Serum Bilirubin and Ferritin Levels Link Between Heme Oxygenase-1 Gene Promoter Polymorphism and Susceptibility to Coronary Artery Disease in Diabetic Patients

¹Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China
³Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China
⁴Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

sjlin{at}vghtpe.gov.tw

ABSTRACT

Objective: Heme oxygenase (HO) leads to the generation of free iron, carbon monoxide, and bilirubin. A length polymorphism of GT repeat in the promoter of human HO-1 gene has been shown to modulate gene transcription. This study aims to assess the association of the length of (GT)n repeats in HO-1 gene promoter with serum bilirubin, markers of iron status, and the development of coronary artery disease (CAD).

Research design and methods: We screened the allelic frequencies of (GT)ⁿ repeats in the HO-1 gene promoter in 986 unrelated individuals that underwent coronary angiography. Serum bilirubin and markers of iron status were evaluated.

Results: The distribution of numbers of (GT)_n repeats was divided into 2 subclasses: class S included shorter (<27) repeats, and class L included longer (27) repeats. Among those with diabetes, subjects with L/L genotype had significantly lower bilirubin levels than those with S/S and S/L genotypes (0.70±0.22 vs. 0.81±0.24 mg/dL, P=0.001) and higher serum ferritin values (4.76±0.72 vs. 4.28±1.05 µg/L for log-ferritin, P=0.001). Compared with those carrying S allele, diabetic subjects with L/L genotype had an almost three-fold increase in CAD risk after controlling for conventional risk factors (odds ratio 2.81, 95% confidence interval [CI] 1.22 to 6.47, P=0.015). Adjusting for both serum bilirubin and ferritin, the effect of HO-1 promoter polymorphism on susceptibility to CAD disappeared.

Conclusions: Length polymorphism in the HO-1 gene promoter is correlated with susceptibility to CAD in diabetic patients and such effect might be conveyed through its influence on serum bilirubin and ferritin.

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