Ala45Thr polymorphism of the NEUROD1 gene and diabetes susceptibility: a meta-analysis

A meta-analysis assessed whether the Ala45Thr polymorphism of the neurogenic differentiation 1 (NEUROD1) gene is associated with increased risk of diabetes mellitus type 1 (T1D) or type 2 (T2D). Fourteen case-control studies were analyzed, including genotype data on 3,057 patients with diabetes (T1D n=1,213, T2D n=1,844) and 2,446 controls. Overall and race-specific summary odds ratios (ORs) were obtained with fixed and random effects models. The Thr allele did not significantly increase the overall risk for T1D (OR 1.27 [0.94-1.71], P=0.12) or T2D (OR 1.07 [0.90-1.28], P=0.46). The Thr allele conferred increased susceptibility in subjects of Asian racial descent to T1D (OR 1.88 [1.10-3.21], P=0.020), but not to T2D (OR 1.08 [0.74-1.56], P=0.70). There was no association in subjects of European descent (OR 0.97 [0.76-1.23], P=0.80 for T1D; OR 1.03 [0.88-1.21], P=0.68 for T2D). Larger studies seemed to show more conservative estimates for the association with T1D (P=0.083). The Ala45Thr polymorphism of the NEUROD1 gene has no effect on susceptibility to T2D. It may however be a risk factor for susceptibility to T1D, in particular for subjects of Asian descent, although bias cannot be totally excluded.