Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
PLoS One. 2011 May 12;6(5):e19587. doi: 10.1371/journal.pone.0019587.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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). Five SNPs were genotyped in the replication study. The spherical equivalent of subjects with high myopia was ≤-8.0 dioptres. The PLINK package was used for genetic data analysis. 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 = 3.54×10(-10), 4.06×10(-11) and 1.56×10(-18) for Group 1, Group 2 and Combined Group, respectively) and the 3-SNP haplotype window composed of rs3026393, rs1506 and rs12421026 (P = 5.48×10(-10), 7.93×10(-12) and 6.28×10(-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/SIGNIFICANCE: PAX6 haplotypes are associated with susceptibility to the development of high myopia in Chinese. The PAX6 locus plays a role in high myopia.
配对盒 6 (PAX6)基因被认为是眼睛发育的主基因。几项研究表明,近视与 11p13 染色体上的 PAX6 区域有关联,但迄今为止,近视与 PAX6 之间的关联结果并不一致。
方法/主要发现:我们在一项初始研究中对 300 例高度近视病例和 300 例对照者(第 1 组)的 PAX6 基因及其调控区的 16 个单核苷酸多态性(SNP)进行了基因分型,并成功地用另一个独立的 299 例高度近视病例和 299 例对照者(第 2 组)进行了复制。在复制研究中,对 5 个 SNP 进行了基因分型。研究对象的等效球镜值≤-8.0 屈光度。使用 PLINK 软件包进行遗传数据分析。没有发现 SNP 与高度近视有关。然而,穷尽滑动窗口单体型分析突出了 rs12421026 的重要作用,因为含有该 SNP 的单体型与高度近视有关。最显著的结果是由包含 rs2071754、rs3026393、rs1506 和 rs12421026 的 4-SNP 单体型窗口给出的(第 1 组、第 2 组和合并组的 P 值分别为 3.54×10(-10)、4.06×10(-11)和 1.56×10(-18))和由 rs3026393、rs1506 和 rs12421026 组成的 3-SNP 单体型窗口(第 1 组、第 2 组和合并组的 P 值分别为 5.48×10(-10)、7.93×10(-12)和 6.28×10(-23))。通过置换进行多次比较校正后,结果仍然具有统计学意义。在这项研究中,还成功地复制了之前研究中发现的相关单体型。
结论/意义:PAX6 单体型与中国人高度近视易感性有关。PAX6 基因座在高度近视中起作用。