Analysis of 14 Candidate Genes for Diabetic Nephropathy on Chromosome 3q in European Populations

Strongest Evidence for Association With a Variant in the Promoter Region of the Adiponectin Gene

  1. Nathalie Vionnet1,
  2. David Tregouët1,
  3. Gbenga Kazeem2,
  4. Ivo Gut3,
  5. Per-Henrik Groop45,
  6. Lise Tarnow6,
  7. Hans-Henrik Parving6,
  8. Samy Hadjadj7,
  9. Carol Forsblom45,
  10. Martin Farrall2,
  11. Dominique Gauguier2,
  12. Roger Cox8,
  13. Fumihiko Matsuda3,
  14. Simon Heath3,
  15. Alexandre Thévard1,
  16. Rachel Rousseau1,
  17. François Cambien1,
  18. Michel Marre910 and
  19. Mark Lathrop3
  1. 1L’Institut National de la Santé et de la Recherche Médicale (INSERM), U525, Université Pierre et Marie Curie-Paris6, Paris, France
  2. 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K
  3. 3Centre National de Génotypage, Evry, France
  4. 4Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
  5. 5Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  6. 6Steno Diabetes Centre, Copenhagen, Denmark
  7. 7Endocrinology-Diabetology Department, INSERM ERM 324, Poitiers Hospital, Poitiers, France
  8. 8Mammalian Research Council, Oxford, U.K
  9. 9Department of Diabetology, Bichat Hospital, Paris, France
  10. 10INSERM U695, Xavier Bichat University of Medicine, Paris, France
  1. Address correspondence and reprint requests to Nathalie Vionnet, INSERM U525, Centre National de Génotypage, 2, Rue Gaston Crémieux, 91006 Evry Cedex, France. E-mail: vionnet{at}cng.fr

Abstract

Linkage studies have mapped loci for diabetic nephropathy and associated phenotypes on chromosome 3q. We studied 14 plausible candidate genes in the linkage region because of their potential role in vascular complications. In a large-scale study of patients from Denmark, Finland, and France who have type 1 diabetes, 1,057 case and 1,127 control subjects, as well as 532 trios, were investigated for association with diabetic nephropathy. We analyzed 69 haplotype-tagging single nucleotide polymorphisms and nonsynonymous variants that were identified by sequencing. Polymorphisms in three genes, glucose transporter 2 (SLC2A2), kininogen (KNG1), and adiponectin (ADIPOQ), showed nominal association with diabetic nephropathy in single-point analysis. The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66–0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03–1.32], P = 0.016; 1.46 [1.11–1.93], P = 0.006, respectively). Analyses of the transmission disequilibrium test showed similar trends only for ADIPOQ_prom2GA with the overtransmission of the A-allele to patients with diabetic nephropathy (1.52 [0.86–2.66], P = NS) and of the G-allele to patients without diabetic nephropathy (0.50 [0.27–0.92], P = 0.026). The overall significance for this variant (nominal P = 0.011) suggests that ADIPOQ might be involved in the development of diabetic nephropathy.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

  • 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.

    • Accepted August 1, 2006.
    • Received February 27, 2006.
« Previous | Next Article »Table of Contents

This Article

  1. doi: 10.2337/db06-0271 Diabetes November 2006 vol. 55 no. 11 3166-3174
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix

Current Issue

  1. December 2009, 58 (12)
    Current Issue
  1. Alert me to new issues of Diabetes