A Disease Haplotype for Advanced Nephropathy in Type 2 Diabetes at the ACE Locus
- Daniel P.K. Ng1234,
- Grzegorz Placha345,
- Serena Choo12,
- Kee-seng Chia12,
- James H. Warram34 and
- Andrzej S. Krolewski34
- 1Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore
- 2Centre for Molecular Epidemiology, National University of Singapore, Singapore
- 3Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts
- 4Department of Medicine, Harvard Medical School, Boston, Massachusetts
- 5Department of Hypertension, Warsaw Medical University, Warsaw, Poland
- Address correspondence and reprint requests to Andrzej S. Krolewski, MD, PhD, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: andrzej.krolewski{at}joslin.harvard.edu
Abstract
Previous investigations of the ACE gene as a susceptibility factor for diabetic nephropathy have primarily focused on its insertion/deletion (Ins/Del) polymorphism. In a departure from these earlier studies, we used three tagging markers (A-5466C, T-3892C, and Ins/Del) at the ACE locus to test for disease haplotype associations. A case-control study design was used where case subjects were type 2 diabetic patients with advanced diabetic nephropathy, as indicated by the presence of proteinuria or chronic renal failure/end-stage renal disease, while control subjects were normoalbuminuric, despite >6 years of diabetes. None of the individual markers showed significant disease association when considered on their own. However, haplotype analyses revealed a near doubling in the prevalence of the A.T.D risk haplotype in case subjects (0.136) compared with control subjects (0.075) (P = 0.009), thus providing first evidence for a disease haplotype for advanced diabetic nephropathy at the ACE locus.
- ACR, albumin-to-creatinine ratio
- CRF, chronic renal failure
- ESRD, end-stage renal disease
- Ins/Del, insertion/deletion
- MAF, minor allele frequency
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted June 21, 2006.
- Received April 13, 2006.
- DIABETES
