Keratoconus (KTCN) is a non-inflammatory corneal thinning disorder and the major cause of cornea transplantations in Western countries. Despite intensive biochemical and genetic investigations, its underlying cause(s) remains poorly understood. Many disease associated loci have been reported based on family studies. Although it has been suggested that mutations in VSX1 and SOD1 may contribute to disease presentation in some cases, the contribution of these genes to keratoconus status is controversial. Other candidate genes for KTCN, such as genes that encode collagens, matrix metalloproteinases, and tissue inhibitors of matrix metaloproteinases, have been examined and excluded as causative genes. Genome-wide association studies (GWAS) aim to identify single nucleotide polymorphisms (SNPs) whose allele frequencies differ significantly between cases and controls. A GWAS on Caucasian keratoconus patients (#596) and controls (#3842) identified 15 potentially associated SNPs. To replicate these findings, these variant SNPs were assessed in another study on Australian Caucasian cases (#524) and controls (#2761). This second study showed that only SNP rs4954218 positioned near the RAB3GAP1 gene was significantly associated with keratoconus. Here, we aimed to investigate the possible association between SNP rs4954218 and keratoconus in Iranians.

165 unrelated Iranian keratoconus patients and 379 unaffected Iranian controls were recruited. Keratoconus was diagnosed based on clinical indications during slit-lamp biomicroscopy, refraction and fundus examination. DNA was extracted from peripheral leukocytes and the SNP rs4954218 was assessed using an allele-specific PCR protocol.

Eleven individuals among the 165 cases and 19 individuals among the 379 controls were carriers of the low frequency allele (G). The difference in frequency of cases and controls with the G allele was not statistically significant (p = 0.4374). Interestingly, the frequency of the G allele of SNP rs4954218 among the Iranian controls studied (0.025) was much lower than the frequency in the Caucasian controls of the previous two studies (0.27). The low frequency of this allele has also been reported in some other populations.

This results suggests an absence of association between the SNP and keratoconus in the Iranian population.