Association of PAX6 Polymorphisms with High Myopia in Han Chinese Nuclear Families

PURPOSE. The paired box 6 (PAX6) gene is critical to eye development. Based on prior linkage evidence, this study was conducted to investigate the association of PAX6 polymorphisms with high myopia in a Han Chinese population. METHODS. Tag single nucleotide polymorphisms (tSNPs) in the PAX6 locus were selected based on HapMap data, and other polymorphisms in its functional regions were also identified. Both tSNPs and identified variants were genotyped in 164 nuclear families with 170 highly myopic (spherical equivalent < -6.0 D in both eyes) offspring. The linkage disequilibrium pattern of SNPs was established in the parental group (n = 328). Family-based association tests were performed using family-based association testing (FBAT) and genetic association computer analyses. RESULTS. Single marker analysis of SNPs rs3026390 and rs3026393 showed significant association with high myopia as a qualitative trait in dominant and recessive models (P = 0.0014 and P = 0.0011, respectively). For rs3026393, the genotype relative risk was 2.57 for G/T and 2.22 for T/T with reference to G/G. Significantly increased transmission was demonstrated for the haplotypes carrying allele T of rs3026393 in the additive and dominant models (P < 0.0070), whereas significantly decreased transmission was found for haplotypes carrying allele G of rs3026393 in the recessive model (P = 0.0173). Preferential transmission of single alleles and haplotypes remained significant after correction for multiple comparisons. CONCLUSIONS. This study demonstrates the association of PAX6 variants with susceptibility to high myopia. The PAX6 locus may contain polymorphisms playing a role in high myopia in southern Han Chinese. (Invest Ophthalmol Vis Sci. 2009; 50: 47-56) DOI: 10.1167/iovs.07-0813