The impact of IGF1R SNPs on susceptibility to age-related cataract

Abstract Background: The insulin-like growth factor 1 receptor (IGF1R) gene is essential for lens development, but the impact of IGF1R on age-related cataract(ARC) has not been investigated. This study explored the association between IGF1R single nucleotide polymorphism (SNP) and ARC susceptibility ,and uncover the underlying mechanism in human lens epithelial (HLE) cells. Methods:A total of 1190 unrelated participants ,comprising 690 ARC patients and 550 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The X2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, in the IGF1R knockdown HLE cells, cell proliferation was detected via CCK-8 analysis. Cell cycle and apoptosis were evaluated by flow cytometry,while the expression of cycle- and apoptosis-related molecules were determined via Q-PCR and Western blot. The Caspase-3 activity was measured using its assay kit. Results: The rs1546713 in IGF1R gene was identified（P =0.046，OR：1.606，CI：1.245,2.071）,which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrest at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclinA , cyclinB, cyclinE and P21,while the pro-apoptosis function was related to stimulate the activation of Caspase-3 activities and the alteration of Caspase-3,Bcl-2 and Bax expression levels. Conclusions: This study first reported that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provided new clues to understanding the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.