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R. Metlapally, K.-N. Tran-Viet, T. L. Yanovitch, A. Bulusu, T. R. White, G. R. Czaja, B. Zhao, Y.-J. Li, T. L. Young; Screening of COL1A1 and COL2A1 Genes for Genetic Association in High-Grade Myopia Multiplex Families. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6088. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Collagen involvement in myopia development via scleral extracellular matrix remodeling leading to ocular elongation is well known. Sclera is comprised of several collagens, with type I collagen being the most prevalent. Recently, COL1A1 single nucleotide polymorphisms (SNPs) were reported to be associated with high-grade myopia in a Japanese case-control cohort, and COL2A1 gene SNPs have been associated with common myopia in a predominantly Caucasian case-control cohort. We investigated whether COL1A1 and COL2A1 polymorphisms are associated with high-grade myopia in a large Caucasian family dataset.
A total of 146 multiplex high-grade myopia families participated in the study. High-grade myopia was defined as ≤ - 5.00 diopters (D) spherical equivalent. Gene tagging SNPs were selected based on a Pearson correlation (r2) of at least 0.67 in the linkage disequilibrium bins, and a minor allele frequency of at least 5% in the Caucasian population, using information in the HapMap database. In all, 8 SNPs were selected for COL1A1 and 14 SNPs were selected for COL2A1. Custom TaqMan® allelic discrimination assays, consisting of a mix of unlabeled polymerase chain reaction primers and the TaqMan® minor groove binding group probe, were designed to genotype the selected SNPs. Pedigree disequilibrium test (PDT) and the association test in the presence of linkage (APL) were used for association analyses.
Both PDT and APL analyses identified significant association between four SNPs (rs1034762, rs1635529, rs1793933, rs3803183) of the COL2A1 gene and high-grade myopia status with p-value less than 0.046 (min p=0.008). Analysis of the COL2A1 SNPs with mild to moderate myopia (-0.50 D to -5.00 D) subjects revealed no significant association. However, analysis with myopia status set at ≤ -0.50 D (mild, moderate, and high-grade myopia groups combined) revealed significant association of the same 4 SNPs (min p=0.005), indicating majority contribution from the high myopia subset. No significant association was found with COL1A1 SNPs and any degree of myopia in the dataset.
In summary, our findings suggest that COL2A1 gene polymorphisms may contribute to high-grade myopia development in Caucasians. COL1A1 gene SNPs were not associated with high-grade myopia in our dataset, indicating possible heterogeneity across different ethnicities.
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