van der Sman-de Beer F et al. (2005) ACE I/D polymorphism is associated with mortality in a cohort study of patients starting with dialysis. Kidney Int 68: 2237–2243

The gene encoding angiotensin-converting enzyme (ACE) bears a diallelic, insertion/deletion (I/D) polymorphism within intron 16. The ACE I/D genotype is thought to be a determinant of plasma and tissue ACE levels, and has been linked to cardiovascular risk and renal disease progression. A recent study has looked at the relationship between ACE I/D genotype and mortality in a group of end-stage renal disease patients starting dialysis.

All 453 participants were drawn from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). A blood sample was taken from each patient around the time that chronic dialysis treatment was started, which was used to determine the ACE I/D genotype. Half of the patients were shown to bear one I allele and one D allele ('ID genotype'), a quarter of the group were homozygous for the I allele ('II genotype'), and a quarter were 'DD' homozygotes.

A total of 154 patients died within the mean follow-up of 2.3 years. Cox regression analysis showed that those with the DD genotype were at a significantly greater risk of death than the II homozygotes (hazard ratio 2.30, 95% CI 1.41–3.75). An intermediate risk was shown in the ID group.

The investigators conclude that the ACE DD genotype is linked to increased mortality in patients starting dialysis. They also explain that, as the I/D polymorphism lies within an intron, its relationship to mortality is probably mediated by another, closely linked variant.