Rs864745 in JAZF1, an Islet Function Associated Variant, Correlates With Plasma Lipid Levels in Both Type 1 and Type 2 Diabetes Status, but Not Healthy Subjects.

ABSTRACT

Objective: This study aims to reveal the association between JAZF1 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 JAZF1 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 JAZF1 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 JAZF1 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 JAZF1 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.