Journal of Molecular Medicine

, Volume 86, Issue 3, pp 341–348

Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study

  • Stéphane Cauchi
  • Christine Proença
  • Hélène Choquet
  • Stefan Gaget
  • Franck De Graeve
  • Michel Marre
  • Beverley Balkau
  • Jean Tichet
  • David Meyre
  • Martine Vaxillaire
  • Philippe Froguel
  • D.E.S.I.R. Study Group
Rapid Communication

DOI: 10.1007/s00109-007-0295-x

Cite this article as:
Cauchi, S., Proença, C., Choquet, H. et al. J Mol Med (2008) 86: 341. doi:10.1007/s00109-007-0295-x

Abstract

Recently, Genome Wide Association (GWA) studies identified novel single nucleotide polymorphisms (SNPs), highly associated with type 2 diabetes (T2D) in several case-control studies of European descent. However, the impact of these markers on glucose homeostasis in a population-based study remains to be clarified.

The French prospective D.E.S.I.R. study (N = 4,707) was genotyped for 22 polymorphisms within 14 loci showing nominal to strong association with T2D in recently published GWA analyses (CDKAL1, IGFBP2, CDKN2A/2B, EXT2, HHEX, LOC646279, SLC30A8, MMP26, KCTD12, LDLR, CAMTA1, LOC38776, NGN3 and CXCR4). We assessed their effects on quantitative traits related to glucose homeostasis in 4,283 normoglycemic middle-aged participants at baseline and their contribution to T2D incidence during 9 years of follow-up.

Individuals carrying T2D risk alleles of CDKAL1 or SLC30A8 had lower fasting plasma insulin level (rs7756992 P = 0.003) or lower basal insulin secretion (rs13266634 P = 0.0005), respectively, than non-carriers. Furthermore, NGN3 and MMP26 risk alleles associated with higher fasting plasma glucose levels (rs10823406 P = 0.01 and rs2499953 P = 0.04, respectively). However, for these SNPs, only modest associations were found with a higher incidence of T2D: hazard ratios of 2.03 [1.00–4.11] for MMP26 (rs2499953 P = 0.05) and 1.33 [1.02–1.73] for NGN3 (rs10823406 P = 0.03).

We confirmed deleterious effects of SLC30A8, CDKAL1, NGN3 and MMP26 risk alleles on glucose homeostasis in the D.E.S.I.R. prospective cohort. However, in contrast to TCF7L2, the contribution of novel loci to T2D incidence seems only modest in the general middle-aged French population and should be replicated in larger cohorts.

Keywords

DiabetesGeneticsMetabolicDisease

Supplementary material

109_2007_295_MOESM1_ESM.doc (36 kb)
Supplementary Table 1Clinical characteristics of the D.E.S.I.R. population at baseline (DOC 36.0 KB)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Stéphane Cauchi
    • 1
  • Christine Proença
    • 1
  • Hélène Choquet
    • 1
  • Stefan Gaget
    • 1
  • Franck De Graeve
    • 1
  • Michel Marre
    • 2
    • 3
  • Beverley Balkau
    • 4
    • 5
  • Jean Tichet
    • 6
  • David Meyre
    • 1
  • Martine Vaxillaire
    • 1
  • Philippe Froguel
    • 1
    • 7
  • D.E.S.I.R. Study Group
    • 6
  1. 1.CNRS 8090-Institute of BiologyPasteur InstituteLilleFrance
  2. 2.René Diderot-Paris 7 UniversityParisFrance
  3. 3.Department of Endocrinology-Diabetology and NutritionBichat Claude Bernard HospitalParisFrance
  4. 4.INSERM U780-IFR69VillejuifFrance
  5. 5.University of Paris-SudParisFrance
  6. 6.Regional Institute for HealthLa RicheFrance
  7. 7.Imperial College, Section of Genomic MedicineImperial College London, Hammersmith HospitalLondonUK