Association of angiotensin-converting enzyme gene dimorphisms with severity of lupus disease

Angiotensin-converting enzyme (ACE) plays an important role in the development of systemic lupus erythematosus (SLE) because its end-product, angiotensin II, plays an integral role in the regulatory system responsible for endothelial control and vascular tone, systems that are commonly affected in patients with SLE. Additionally, ACE inhibitors have been shown to retard the progression of SLE and lupus nephritis. Our goal was to investigate whether ACE gene polymorphisms are associated with increasing severity of SLE. We genotyped 39 SLE patients of varying disease severity from a homogenous Asian population and 79 control subjects for ACE I/D and 2350 G > A dimorphisms. All patients met the American College of Rheumatology (ACR) criteria for SLE and their disease severity was measured using Systemic Lupus Activity Measure (SLAM). The "A" allele was found to be associated with increase in severity of SLE with the AA genotype present only in severe disease. No association with SLE in general, compared to healthy subjects, was found with either dimorphism. We also examined the transmission of haplotypes as defined by these polymorphisms. The D and A alleles were found in strong linkage disequilibrium especially in severe SLE. The DA-haplotype was more frequent in severe SLE, than mild to moderate disease. Our findings suggest that DNA sequence variation in the ACE gene influences disease progression and severity of SLE.