The Absence of Association Between MYOC or c-MET Polymorphisms and High-Myopia in a Caucasian Family-Based Cohort

Abstract

Purpose: : Both myocilin gene (MYOC) and hepatocyte growth factor (HGF) polymorphisms have been previously associated with high-myopia in Asian populations. MYOC encodes the structural protein, myocilin. Mutations of MYOC have been related to the development of glaucoma which, in turn, has been linked to increased intraocular pressures and myopia. HGF activates many cell signaling pathways by binding to the tyrosine kinase receptor, c-MET. The results from previous association studies and the functions of c-MET and MYOC make these genes ideal candidates for high-myopia. The primary aim of this study was to determine if these associations were present in a Caucasian family-based cohort biased towards high-myopia.

Methods: : A total of 146 multiplex families, consisting of 679 subjects, were included. We analyzed two datasets with high myopia defined by -5.0 diopters (D) for sphere and spherical equivalence (SE), respectively. The control refractive error was defined as >-0.5D. Tagging SNPs were selected by SNPSelector^® program conditional on Pearson correlation (r²) <0.67 and a minor allele frequency >5% in Caucasian population. Using Taqman^® allelic discrimination assays, genotyping was performed for 9 SNPs on MYOC and 6 SNPs on c-MET, including all of the significant SNPs from previous studies. Family-based pedigree disequilibrium test (PDT), genotypic PDT and association test in the presence of linkage (APL) were used to test association between markers and high myopia. Statistical significance was defined as a p-value <0.05.

Results: : All c-MET markers did not reach significance level in all analyses (min p-value = 0.178). Some borderline p-values were observed for MYOC including rs2421853 (APL p=0.042) for the dataset defined by sphere and rs12076134 (PDT p=0.047) and rs2421853 (APL p=0.033) for the dataset defined by SE. These markers are not significant after correcting for multiple testing.

Keywords: myopia • candidate gene analysis • genetics