Rs864745 in , an Islet Function Associated Variant, Correlates With Plasma Lipid Levels in Both Type 1 and Type 2 Diabetes Status, but Not Healthy Subjects.

OBJECTIVE

This study aims to reveal the association between rs864745 A>G variant and type 2 diabetes (T2D), type 1 diabetes (T1D) risk, and their correlation with clinical features, including islet function, islet autoimmunity, and plasma lipid levels.

METHODS

We included 2505 healthy controls based on oral glucose tolerance test (OGTT), 1736 unrelated T2D, and 1003 unrelated autoantibody-positive T1D individuals. Binary logistic regression was performed to evaluate the relationships between rs864745 in and T2D, T1D, and islet-specific autoantibody status under the additive model, while multiple linear regression was used to assess its effect on glycemic-related quantitative traits and plasma lipid levels.

RESULTS

We did not find any association between rs864745 in and T2D, T1D, or their subgroups (All P > 0.05). For glycemic traits, we found that the G allele of this variant was significantly associated with higher 120 min insulin level, insulinogenic index (IGI), corrected insulin response (CIR), and acute insulin response (BIGTT-AIR) (P = 0.033, 0.006, 0.009, and 0.016, respectively) in healthy individuals. Similar associations were observed in newly diagnosed T2D but not T1D individuals. Although this variant had no impact on islet autoimmunity (All P > 0.05), significant associations with plasma total cholesterol (TC) and low-density lipoprotein (LDL) level stratified by rs864745 variant were observed in the disease status of T2D (P = 0.002 and 0.003) and T1D (P = 0.024 and 0.009), with significant heterogeneity to healthy individuals.

CONCLUSIONS

The common rs864745 variant contributes to islet function and lipid metabolism, which might be put into genetic risk scores to assess the risk of related clinical features.