The association study between MTOR and high myopia

Myopia, in particular high myopia (HM), is a major global ocular disorder and genetic factors playing a crucial role in its development. This study aimed to shed light on the genetic association between candidate single nucleotide polymorphisms (SNPs) and HM, offering insights into the mechanisms underlying HM.

This case-control study involves 1008 unrelated Han Chinese participants, including 508 HM patients and 500 healthy controls. Eleven candidate SNPs that were previously linked to refractive errors in other populations were genotyped using multiplex polymerase chain reaction and high-throughput sequencing. We analyzed the associations between SNPs and HM under five genetic models, adjusting for age and sex. Ocular biometrics, such as axial length (AL) and refractive error, were correlated with the significant SNPs identified. We conducted functional annotation of the target SNP using bioinformatic tools. In addition, a form-deprivation myopia mouse model was employed to validate the role of the candidate gene through Western blot analysis of retinal proteins.

Among the 11 SNPs analyzed, rs17036350 in the Mechanistic Target of Rapamycin Kinase (MTOR) gene showed a significant association with HM in the Southern Han Chinese population. Under the heterozygous model, the results for this SNP suggest an association with high myopia (P=0.032, OR=0.727, 95% CI: 0.542-0.975). In individuals with HM, carriers of the C allele of rs17036350 (CC + CT genotypes) had a significantly longer AL than those with the TT genotype (P=0.015), and the association was more pronounced in female patients (P=0.033). Bioinformatics functional analysis revealed that rs17036350 interacts with the MTOR gene in a chromatin regulatory loop, which potentially enhances the transcription factor PBX1 and downstream gene expression. Myopic eyes exhibited significant axial elongation in the FDM mouse model, and elevated levels of phosphorylated mTOR (p-mTOR) were observed in the retina compared to controls (P=0.0128).

This study suggested that rs17036350 within MTOR is potentially a genetic marker associated with HM in the Southern Han Chinese population, and showed a specific association with AL. Additionally, MTOR activation may contribute to axial elongation in myopia. These findings provide new insights into the genetic regulation of refractive development and support potential targeted strategies for managing myopia.