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.