Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies

Abstract

Inflammation and genetics are both prominent mechanisms in the pathogenesis of atherosclerosis and arterial thrombosis. Accordingly, a number of population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules tumour necrosis factors (TNF) alpha and beta, transforming growth factors (TGF) beta1 and 2, interleukin (IL) 1 and its receptor antagonist (IL 1ra), CD14 (the receptor for lipopolysaccharide), P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Although they are very preliminary and partly conflicting, the data provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of ischaemic heart disease.

Figure 1

Simplified representation of the role of inflammatory molecules in atherogenesis. Injured endothelial cells (for example, by oxidised low density lipoprotein (LDL), cytokines, or lipopolysaccharide) produce cytokines (for example, interleukin (IL) 1), which stimulate the expression of adhesion proteins on the endothelial surface (for example, selectins and cell adhesion molecules). The latter recruit circulating leucocytes into the subendothelial space. Further cytokine release by infiltrated monocyte/macrophages (Mφ) and T lymphocytes promotes the formation of foam cells and the migration of smooth muscle cells from the media. The proinflammatory effects of IL 1 and tumour necrosis factor (TNF) are counterbalanced by the modulatory effects of transforming growth factor (TGF) produced by connective tissue cells. ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule.