Purpose: The collagen type I alpha 1 (COL1A1) gene was recently reported to be associated with high myopia in the Japanese population. To validate this positive association, the tag single-nucleotide polymorphism (tSNP) approach was used.
Methods: Eight tSNPs, including rs2075555 and rs2269336 (previously reported to be high myopia-susceptible SNPs in the Japanese), were selected to tag the linkage disequilibrium blocks harboring the COL1A1. These tSNPs were genotyped by using an SNP assay. A total of 427 unrelated Japanese cases with high myopia (axial length, >or=26.50 mm in both eyes; the refraction of the 644 phakic eyes ranged from -5.0 to -36.0 D, with a mean +/- SD of -13.61+/-4.20 D) and 420 Japanese control subjects were recruited. Genotype and allele distributions were compared between the cases and controls by using the chi(2) test, with multiple testing corrections performed by the permutation test.
Results: There was no association noted between high myopia and rs2075555 (P=0.47, P(c)>0.99) and rs2269336 (P=0.40, P(c)>0.99). Meta-analysis of a previous Japanese study and new data obtained in a fixed-effect model indicated a mild significant association of high myopia with rs2075555 (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.03-1.38, P=0.022) and rs2269336 (OR, 1.18; 95% CI, 1.02-1.36, P=0.026). No significant associations were seen with further tSNPs tests.
Conclusions: This study did not replicate the previously reported positive association between COL1A1 and high myopia in the Japanese population, and thus the genetic risk associated with this gene, if any, is weaker than originally reported.