Vascular injury in systemic sclerosis: angiotensin-converting enzyme insertion/deletion polymorphism

Abstract

The microvascular involvement in systemic sclerosis (SSc) is characterized by endothelial damage and smooth muscle cell migration in the intima. The vascular pathologic modifications in SSc are strikingly similar to those of atherosclerosis. SSc also is characterized by an accelerated macrovascular disease. The gene encoding for angiotensin-converting enzyme (ACE) is a 21-kb, 26-exon gene, localized on chromosome 17 (17q23). Polymorphic sites are an insertion/deletion (I/D) that consists of three genotypes: DD and II homozygotes, and ID heterozygote. ACE gene polymorphisms have been linked to vascular disorders (coronary artery disease, hypertension, cerebrovascular disease, hypertrophic cardiomyopathy, and diabetic or nondiabetic nephropathy). In particular, the possession of ACE D allele was associated with an increased risk of developing malignant vascular injury. ACE D allele frequency of the I/D polymorphism was associated with an increased risk of SSc, suggesting a genetic contribution to the disease. The discrepancy between the high prevalence of D allele and reduced ACE plasma levels in SSc demonstrate the lack of knowledge on the regulation and function of renin-angiotensin system in SSc.