Details

Autor(en) / Beteiligte

• Cauchi, Stéphane
• Proença, Christine
• Choquet, Hélène
• Gaget, Stefan
• De Graeve, Franck
• Marre, Michel
• Balkau, Beverley
• Tichet, Jean
• Meyre, David
• Vaxillaire, Martine
• Froguel, Philippe

Titel

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

Ist Teil von

• Journal of molecular medicine (Berlin, Germany), 2008-03, Vol.86 (3), p.341-348

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.