Genetic Association of Insulin-Like Growth Factor-1 Polymorphisms With High-Grade Myopia in an International Family Cohort

Abstract

Purpose: : Evidence from human myopia genetic mapping studies (MYP3 locus), modulated animal models, and observations of glycemic control in humans suggests that insulin-like growth factor-1 (IGF-1) may play a role in the control of eye growth. We examined whether IGF-1 polymorphisms were associated with myopia in an international, large dataset of Caucasian high-grade myopia pedigrees.

Methods: : 265 multiplex families with 1391 subjects participated in the study. IGF-1 genotyping was performed with thirteen selected tagging single nucleotide polymorphisms (SNPs) using Taqman^TM allelic discrimination assays. Family-based pedigree disequilibrium test (PDT) was performed to test for association. Myopia status was defined using sphere (SPH) or spherical equivalent (SE) and analyses assessed the association of: 1) high-grade myopia (≤-5.00D), 2) moderate and low myopia (-0.50 to -5.00D), and 3) any myopia (≤-0.50D) with IGF-1 markers. Results were declared significant if the p-value was ≤ 0.0038 based on Bonferroni correction. Q-values that take into account multiple testing were also obtained.

Results: : In all, three SNPs - rs10860860, rs2946834, and rs6214 - showed p-values less than 0.05. SNP rs6214 showed positive association with the ‘high-grade’ (p=2 x 10^-3) and ‘any’ myopia groups (p=2 x 10^-3) after correcting for multiple testing. The ‘low and moderate’ myopia group showed no association with all IGF-1 SNPs tested.

Conclusions: : Our study supports a genetic association between IGF-1 and high-grade myopia. These findings are in line with recent evidence in an experimental myopia model showing that IGF-1 promotes ocular growth and axial myopia. IGF-1 may be a potential myopia candidate gene for further investigations.

Keywords: myopia • gene screening • genetics