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Effects of INSR genetic polymorphism on hippocampal volume and episodic memory in chinese type 2 diabetes
Xin Du1, Yang Zhang1, Qiuyue Zhao1
1Department of Medical imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Aims:
We aimed to investigate the effect of the type 2 diabetes-specific insulin/IGF signaling genetic variants on the hippocampal volume and their relationships with episodic memory in Chinese patients with type 2 diabetes.
Methods:
Analysis of variance was used to evaluate the genotype-by-diagnosis interaction effect on hippocampal volume in Chinese participants (109 patients with type 2 diabetes, 116 healthy controls). Mediation analysis was performed to test whether the hippocampal volume would mediate the association between genotype and episodic memory in patients with type 2 diabetes.
Results:
INSR (rs8101064) exhibited a significant genotype-by-diagnosis interaction effect on the bilateral hippocampal volumes (left, P = 0.020; right, P = 0.004, PFDR < 0.05). The T allele carriers exhibited smaller bilateral hippocampal volumes than the CC homozygotes in patients with type 2 diabetes (left, P = 0.004; right, P = 0.002). Mediation analysis revealed the significant mediation effect of the left hippocampal volume on the association between INSR (rs8101064) genetic polymorphism and the short- and long-term memory scores in patients with type 2 diabetes (short-term memory: 95% CI, -2.716, -0.266; long-term memory: 95% CI, -0.823, -0.103).
Conclusions:
Hyperglycemia exposure and INSR (rs8101064) genetic polymorphism had an interaction effect on the hippocampal volume, and the T allele of the INSR (rs8101064) may serve as a risk factor for the decreased hippocampal volume in Chinese patients with type 2 diabetes. The left hippocampal volume mediated the effect of INSR (rs8101064) genetic polymorphism on episodic memory in Chinese patients with type 2 diabetes, which provided a biological pathway for understanding how the INSR (rs8101064) genetic polymorphism affects episodic memory in type 2 diabetes.
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