Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort.

Publications // Young Lab // Sep 01 2010

PubMed ID: 20435602

Author(s): Metlapally R, Ki CS, Li YJ, Tran-Viet KN, Abbott D, Malecaze F, Calvas P, Mackey DA, Rosenberg T, Paget S, Guggenheim JA, Young TL. Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort. Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4476-9. doi: 10.1167/iovs.09-4912. Epub 2010 Apr 30. PMID 20435602

Journal: Investigative Ophthalmology & Visual Science, Volume 51, Issue 9, Sep 2010

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 (IGF)-1 plays a role in the control of eye growth. This study was conducted to determine whether IGF-1 polymorphisms are associated with myopia in a large, international dataset of Caucasian high-grade myopia pedigrees.

METHODS Two hundred sixty-five multiplex families with 1391 subjects participated in the study. IGF-1 genotyping was performed with 13 selected tag single nucleotide polymorphisms (SNPs) using allelic discrimination assays. A 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 (<or=-5.00 D), and (2) any myopia (<or=-0.50 D) with IGF-1 markers. Results were declared significant at P<or=0.0038 after Bonferroni correction. Q values that take into account multiple testing were also obtained.

RESULTS In all, three SNPs-rs10860860, rs2946834, and rs6214-were present at P<0.05. SNP rs6214 showed positive association with both the high-grade- and any-myopia groups (P=2×10(-3) and P=2×10(-3), respectively) after correction for multiple testing.

CONCLUSIONS The 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 myopia candidate gene for further investigation.