Genetic variation at the ACE gene is associated with persistent microalbuminuria and severe nephropathy in type 1 diabetes: the DCCT/EDIC Genetics Study - PubMed (original) (raw)

Genetic variation at the ACE gene is associated with persistent microalbuminuria and severe nephropathy in type 1 diabetes: the DCCT/EDIC Genetics Study

Andrew P Boright et al. Diabetes. 2005 Apr.

Abstract

The development and progression of microvascular complications have been extensively documented in a cohort of type 1 diabetic subjects enrolled in the Diabetes Control and Complications Trial (DCCT) and followed in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. We describe the association of genetic variation in the ACE gene in 1,365 DCCT/EDIC subjects with incident persistent microalbuminuria (n = 312) and severe nephropathy (n = 115). We studied three markers (rs1800764, insertion/deletion, and rs9896208) in the ACE gene that allowed us to capture genetic variation in the common haplotypes occurring at frequencies of >5% in Caucasians. Compared with the more frequent genotype (D/I) for the insertion/deletion polymorphism, in multivariate models, the I/I genotype conferred a lower risk for persistent microalbuminuria (hazard ratio [HR] 0.62 [95% CI 0.43-0.89], P = 0.009) and severe nephropathy (0.56 [0.32-0.96], P = 0.033). Variation at the two other markers, rs1800764 and rs9896208, were also associated with these renal outcomes. In addition, homozygosity for the common haplotype TIC (which corresponded to the T, insertion, and C alleles at the three markers, rs1800764, insertion/deletion, and rs9896208, respectively) versus the CDT/TIC haplotype pair was associated with lower risk for development of persistent microalbuminuria (HR 0.49 [0.32-0.75], P = 0.0009) and severe nephropathy (0.41 [0.22-0.78], P = 0.006). Our findings in the DCCT/EDIC cohort provide strong evidence that genetic variation at the ACE gene is associated with the development of nephropathy in patients with type 1 diabetes.

PubMed Disclaimer

Figures

FIG. 1

FIG. 1

Cumulative incidence of persistent microalbuminuria according to ACE genotype. The time was calculated from DCCT baseline to the first consecutive timed AER collection >20.8 μg/min in the DCCT or EDIC follow-up periods in individuals genotyped for three ACE polymorphisms: rs1800764, insertion/deletion, and rs9896208. For univariate analysis, see Table 2.

Similar articles

Cited by

References

    1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–986. - PubMed
    1. Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia. 1983;25:496–501. - PubMed
    1. Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR. The changing natural history of nephropathy in type I diabetes. Am J Med. 1985;78:785–794. - PubMed
    1. Hovind P, Tarnow L, Rossing K, Rossing P, Eising S, Larsen N, Binder C, Parving HH. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care. 2003;26:1258–1264. - PubMed
    1. Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J. Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of type 1 diabetes: the Linkoping Diabetes Complications Study. Diabetologia. 2004;47:1266–1272. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources