Heme Oxygenase-1 Gene Promoter Polymorphism Is Associated With Coronary Artery Disease in Japanese Patients With Coronary Risk Factors

Abstract

Objective-Heme oxygenase (HO) is important in the defense against oxidative stress and as a factor in an antiatherogenic mechanism. Compared with long (GT) n repeats, short (GT) n repeats in the human HO-1 gene promoter were shown to have higher transcriptional activity in response to oxidative stress. There is a strong link between oxidative stress and the pathogenesis of coronary artery disease (CAD). Methods and Results-We screened the allelic frequencies of (GT) n repeats in the HO-1 gene promoter in 577 patients who underwent coronary angiography. Because the distribution of numbers of (GT) n repeats was bimodal, we divided the alleles into 2 subclasses: class S included shorter (Ͻ27) repeats, and class L included longer (Ն27) repeats. Multivariate logistic regression models including standard coronary risk factors revealed that the genotypes were significantly related to CAD status in hypercholesterolemic, diabetic patients or in smokers. In this study, the patients with shorter GT repeats were less likely to have CAD. Conclusions-Length

Further Evidence That the UGT1A1*28 Allele Is Not Associated with Coronary Heart Disease: The ECTIM Study

“…In connection with this, heme-oxygenase, the rate-limiting enzyme involved in bilirubin production (2 ), may also play an important role. It has been shown that a decreased activity of heme-oxygenase is associated with an increased risk of CHD in patients with coronary risks (6 ). It is also worth noting that hemeoxygenase induces the production of nitric oxide, a powerful and active vasodilator, likely to protect against atherosclerosis.…”

Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers

“…The primers used to generate HO-1 amplicons of 98 -142 bp were sense: 5 0 -AGAGCCTGCAGCTTCT CAGA-3 0 and antisense: 5 0 -ACAAAGTCTGGCCATAGGAC-3 0 (Kaneda et al, 2002). The 5 0 site of the sense primer was labelled with FAM fluorescence dye.…”

“…Reports indicated that these microsatellites are highly polymorphic, and longer (GT) n repeat exhibits lower HO-1 transcriptional activity (Yamada et al, 2000;Chen et al, 2002Chen et al, , 2004Kaneda et al, 2002). Subjects carrying longer (GT) n repeats are associated with the higher susceptibility of cardiovascular or chronic obstructive pulmonary diseases (Yamada et al, 2000;Chen et al, 2002Chen et al, , 2004Kaneda et al, 2002). Oxidative stress is associated with the pathogenesis of cancers (Xie and Huang, 2003).…”

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

“…This is underscored by the observation that a microsatellite polymorphism in the promoter region of the HO-1 gene that is linked to decreased inducibility is associated with restenosis and increased vascular inflammation after percutaneous transluminal angioplasty, susceptibility to coronary artery disease in type 2 diabetic patients and in Japanese patients with coronary risk factors, and the development of abdominal aortic aneurysms (Exner et al, 2001;Chen et al, 2002;Kaneda et al, 2002;Schillinger et al, 2002a,b). Since excessive growth of vascular SMCs is an important contributing factor to a number of vascular disease states, including restenosis following angioplasty, atherosclerosis, and hypertension (Zierler et al, 1982;Ross, 1986;Schwartz et al, 1986), increasing HO-1 expression in blood vessels may offer a promising approach in treating vascular disorders.…”