Candidate gene study to investigate the genetic determinants of normal variation in central corneal thickness.

Purpose: The genetic component underlying variation in central corneal thickness (CCT) in the normal population remains largely unknown. As CCT is an identified risk factor for open-angle glaucoma, understanding the genes involved in CCT determination could improve our understanding of the mechanisms involved in this association.

Methods: To identify novel CCT genes, we selected eight different candidates based on a range of criteria. These included; aquaporin 1 (AQ1), aquaporin 5 (AQ5), decorin (DCN), fibrillin-1 (FBN1), keratocan (KERA), lumican (LUM), osteoglycin (OGN), and paired box 6 (PAX6). Tagging single nucleotide polymorphisms (SNPs) selected from the HapMap database were genotyped to cover the majority of genetic variation within each gene. Each SNP was screened in a large, population-based cohort from Australia and both single SNP and haplotype analyses were undertaken.

Results: Two SNPs were found to be nominally associated with CCT, rs17352842 from FBN1 (p=0.02) and rs3026398 from PAX6 (p=0.02), although neither of these p values survived correction for multiple testing. Haplotype analysis revealed one haplotype within FBN1 (corrected p=0.048) and two haplotypes within PAX6 (strongest corrected p=0.006) associated with CCT. No other SNPs or haplotypes from the remaining genes showed any significant correlation with CCT.

Conclusions: Results from this study suggest that FBN1 and PAX6 are potentially involved in determining CCT. This is the first published study to investigate these genes for association with normal CCT variation.