Association of PAX6 SNPs and Myopia Development in the Singapore Cohort Study of the Risk Factors for Myopia (SCORM)

Abstract

Purpose: : The postnatal role of the PAX6 gene, a fundamental homeobox gene essential for eye development, is unknown, although it is expressed in childhood and adulthood. PAX6 has been suggested as a candidate gene for myopia development, but no association was found in a Cauacasian twin study (Hammond, AJHG 2004). This study aims to examine whether PAX6 is associated with myopia in Asians.

Methods: : Refractive error in the form of spherical equivalent for right eyes (SER) was measured with cycloplegic autorefraction in a cohort of 892 children in Singapore aged 7–9 years at baseline and annually for 3 years. DNA was extracted from buccal scrapes, and the 5 tagged single nucleotide polymorphisms (SNPs) used in the twin study, as well as additional SNPs in flanking regions, were genotyped in these Singapore children. Hierarchical linear modeling techniques were used to analyse the longitudinal data.

Results: : Using "best fit" linear modeling, myopia was significantly associated with age (mean SER decrease 0.71D for each year), time (SER decreased by a mean 1.25D per year) and an age*time interaction (the older the child, the smaller the reduction in SER). Although there was no significant association between individual SNPs and SER, preliminary analyses suggested significant associations with variables denoting the interaction between time and several SNPs (P = 0.01) including new SNPs identified in the flanking gene regions.

Conclusions: : These data suggest that PAX6 may be involved in myopia development in Asians; polymorphisms may mediate growth of the eye. This study emphasises the value of longitudinal data, collected during myopia development, rather than "final outcome" data.

Keywords: myopia • refractive error development • candidate gene analysis