An insertion/deletion polymorphism within the 3'‑untranslated region of COL1A2 confers susceptibility to osteoporosis.

Polymorphisms located in microRNA (miRNA) binding sites may interfere with the interaction between miRNAs and mRNAs, and thereby alter the expression of genes. The current study aimed to investigate the association between an insertion/deletion (INS/DEL) polymorphism in the 3'‑untranslated region (3'‑UTR) of COL1A2 and the risk of developing osteoporosis. In the present study, COL1A2 was identified as a target gene of let‑7g in osteoblast cells obtained from patients, using a luciferase reporter system. This was further confirmed by the observation that exogenous overexpression of let‑7g in the osteoblast cells downregulated the expression of COL1A2 in the cells in the INS/INS group, however not in the DEL/DEL group. In addition, a total of 487 subjects were enrolled in the present study and their bone mineral density (BMD) was measured. The BMD at the four tested sites, the femoral neck, total left hip, L1‑L4 and intertrochanteric areas, were significantly reduced in the INS/DEL or DEL/DEL group compared with the INS/INS group. Furthermore, the levels of COL1A2 and let‑7g were measured in the primary osteoblasts obtained from 48 patients with osteoporosis. While the let‑7g levels were comparable between each genotype group, the expression level of COL1A2 in the DEL/DEL and INS/DEL group was significantly greater compared with the INS/INS group. In conclusion, the present study demonstrated that the INS/DEL polymorphism in the 3'‑UTR of COL1A2 is able to interfere with the interaction between miRNA and mRNA. In addition, it is the first study, to the best of our knowledge, to indicate that the minor allele (Del) is associated with a reduced risk of developing osteoporosis.