Myeloperoxidase gene variation and coronary flow reserve in young healthy men.

Abstract

Chronic inflammation may lead to endothelial dysfunction, which manifests as an impaired coronary reactivity. Impairment in coronary flow reserve (CFR), preceding the clinical symptoms of coronary artery disease, can be measured noninvasively by positron emission tomography. Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism (-463G/A) which affects gene transcription. Whether these variants associate with coronary artery function is not known. Myocardial blood flow at rest and during adenosine-induced hyperemia was assessed in 49 healthy young men with normal or slightly elevated serum total cholesterol. These subjects were divided into high (G/G) and low (A/G, A/A) MPO expression groups and effect of MPO genotype on myocardial blood flow was evaluated. We found a significant difference between MPO genotypes in CFR after adjusting for age, body mass index, smoking and family history of cardiovascular disease (p = 0.019). Men with G/G genotype had 18.1% lower CFR than subjects with low-expression genotypes (A/G and A/A). This was due to an 11.5% lower adenosine-stimulated flow of the G/G genotype carriers (p = 0.049). These findings provide evidence that MPO polymorphism is associated with coronary artery reactivity. However, the number of individuals investigated was low and our observation should be confirmed by a larger number of subjects.