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Diabetes 53:865-869, 2004
© 2004 by the American Diabetes Association, Inc.

Brief Genetics Report

Scrutiny of the Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) Locus Reveals Conserved Haplotype Block Structure not Associated With Diabetic Nephropathy

Daniel P.K. Ng1,2,3, William H. Walker1, Kee-Seng Chia3, Serena Choo3, James H. Warram1, and Andrzej S. Krolewski1,2

1 Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts
2 Department of Medicine, Harvard Medical School, Boston, Massachusetts
3 Community, Occupational and Family Medicine, National University of Singapore, Singapore, Singapore

Glutamine-fructose-6-phosphate transaminase 1 (GFAT) is the rate-limiting enzyme of the hexosamine pathway that has been implicated in the pathogenesis of diabetic nephropathy. As such, we hypothesized that GFPT1, which encodes for GFAT, may confer genetic susceptibility to this complication among Caucasians. Screening of all known functional regions of GFPT1 revealed six single nucleotide polymorphisms (SNPs) that were located in the promoter, introns, and 3' untranslated region. The ~60 kb GFPT1 locus was encompassed in a single conserved haplotype block, and two tagging SNPs were sufficient to capture >90% of the haplotype diversity. Analysis of these SNPs in a case-control study made up of type 1 diabetic subjects (324 case subjects with diabetic nephropathy and 289 control subjects with normoalbuminuria despite >15 years of diabetes) revealed no significant association even after stratification by sex, diabetes duration, glucose control, and blood pressure. Similar results were obtained among type 2 diabetic subjects (202 case and 114 control subjects). Genetic variation in GFPT1 is thus unlikely to have a major impact on susceptibility to diabetic nephropathy.

Address correspondence and reprint requests to Andrzej S. Krolewski, MD, PhD, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Pl., Boston, MA 02215. E-mail: andrzej.krolewski{at}joslin.harvard.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.