Purpose  The paired box 6 (PAX6) gene is considered as a “master gene” for eye development. Linkage of myopia to the PAX6 region on chromosome 11p13 was shown in several studies, but the results for association between myopia and PAX6 were inconsistent so far. We deeply analyse the association between high myopia and PAX6 gene with its regulatory regions in Han Chinese.

Methodology  We genotyped 16 single nucleotide polymorphisms (SNPs) in the PAX6 gene and its regulatory regions in an initial study for 300 high myopia cases and 300 controls (Group 1), and successfully replicated the positive results with another independent group of  299 high myopia cases and 299 controls (Group 2). The spherical equivalent of subjects with high myopia was ≤-8.0 dioptres. The PLINK package was used for genetic data analysis.

Principal Findings  No association was found between each of the SNPs and high myopia. However, exhaustive sliding-window haplotype analysis highlighted an important role for rs12421026 because haplotypes containing this SNP were found to be associated with high myopia. The most significant results were given by the 4-SNP haplotype window consisting of rs2071754, rs3026393, rs1506 and rs12421026 (P=1.55´10^-10, 3.51´10^-11 and 1.76´10^-18 for Group 1, Group 2 and Combined Group, respectively) and the 3-SNP haplotype window composed of rs3026393, rs1506 and rs12421026 (P=3.59´10^-10, 6.57´10^-12 and 6.59´10^-23 for the three respective groups). The results remained significant after correction for multiple comparisons by permutations. The associated haplotyes found in a previous study were also successfully replicated in this study.

Conclusions  PAX6 haplotypes are associated with susceptibility to the development of high myopia in Chinese. The PAX6 locus plays a role in high myopia.