Serum Bilirubin and Ferritin Levels Link Heme Oxygenase-1 Gene Promoter Polymorphism and Susceptibility to Coronary Artery
Disease in Diabetic Patients
Ying-Hwa Chen , MD, PHD 1 , 2 ,
Lee-Young Chau , PHD 3 ,
Jaw-Wen Chen , MD 2 , 4 and
Shing-Jong Lin , MD, PHD 1 , 2 , 4
1 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
2 Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
3 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China
4 Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China
Corresponding author: Shing-Jong Lin, 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 repeats
in the promoter of human HO-1 gene has been shown to modulate gene transcription. The aim of this study was to assess the
association of the length of (GT) n repeats in the 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 who underwent coronary angiography. Serum bilirubin and markers
of iron status were evaluated.
RESULTS —The distribution of numbers of (GT) n repeats was divided into two subclasses: class S included shorter (<27) repeats, and class L included longer (≥27) repeats.
Among those with diabetes, subjects with the 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 the S allele, diabetic subjects with the L/L genotype had an almost threefold increase
in CAD risk after controlling for conventional risk factors (odds ratio 2.81, [95% CI 1.22–6.47], P = 0.015). With adjustment 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 this effect
might be conveyed through its influence on serum bilirubin and ferritin.
Footnotes
Published ahead of print at http://care.diabetesjournals.org on 28 April 2008.
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Serum Bilirubin and Ferritin Levels Link Heme Oxygenase-1 Gene Promoter Polymorphism and Susceptibility to Coronary Artery Disease in Diabetic Patients

10.2337/dc07-2126