The common rs13266634 C > T variant in SLC30A8 contributes to the heterogeneity of phenotype and clinical features of both type 1 and type 2 diabetic subtypes.

Aims: T2D and T1D are phenotypically heterogeneous. This study aims to reveal the relationship between the common SLC30A8 rs13266634 variant and subgroups of T2D and T1D and their clinical characteristics.

Methods: We included 3158 OGTT-based healthy controls, unrelated 1754 T2D, and 1675 autoantibody-positive T1D individuals. The associations between rs13266634 and subtypes of T2D, T1D, autoantibody status and glycemic-related quantitative traits were performed by binary logistic regression analysis under the additive model and multiple linear regression with appropriate adjustment.

Results: We found that the T allele of rs13266634 was protectively associated with lean (OR = 0.810, P = 6.91E-04) but not obese T2D with considerable heterogeneity (P = 0.018). This allele also conferred significant protection with T1D of single (OR = 0.847, P = 9.76E-03), but not multi autoantibodies with substantial heterogeneity (P = 0.005). This variant significantly affected OGTT-related insulin release in lean (P = 2.66E-03, 3.88E-03 for CIR and DI, respectively) but not obese healthy individuals. Furthermore, rs13266634 T allele correlated with the risk of ZnT8A (OR = 1.440, P = 3.31E-05) and IA-2A (OR = 1.219, P = 1.32E-03) positivity, with more effect size in children/adolescents compared with adult-onset T1D subtypes.

Conclusions: These suggested that the SLC30A8 rs13266634 variant might be put into genetic risk scores to assess the risk of the subtypes of T1D and T2D and their related clinical features.