Role of extracellular matrix remodelling gene SNPs in keratoconus.

Introduction

Single nucleotide polymorphisms (SNPs) in genes for certain structural components may be implicated in the pathogenesis of keratoconus. We hypothesized links between SNPs in genes coding for collagen, matrix metalloproteinase 9 (MMP9) and tissue inhibitor of matrix metalloproteinase (TIMP) and keratoconus. Furthermore, we hypothesized links between MMP-9 and TIMP-1 SNPs and their tear level in keratoconus patients.Materials and methods: We genotyped 200 keratoconus and 100 control subjects by allele-specific PCR, and quantified MMP-9 and TIMP1 in tear samples by ELISA.

Results

COL4A3 (rs55703767) and MMP-9 (rs17576) G alleles were over-represented in keratoconus patients (P < 0.01). TIMP-1 (rs6609533) A allele was more prevalent in keratoconus females (P < 0.01) but not in males (P = 0.73). MMP-9 was higher (P < 0.001) and TIMP1 lower (P < 0.001) in tear samples from keratoconus patients compared to controls. Keratoconus cases carrying MMP-9 (rs17576) homozygous (GG) alleles had higher tear MMP-9 compared to those carrying the (A) allele (P < 0.01). Females carrying TIMP-1 (rs6609533) homozygous (AA) alleles in both groups had significantly lower tear TIMP-1 compared to carriers of the AG and GG genotypes.

Conclusions

This study supports the hypothesis of a functional role for COL4A3 (rs55703767, G/T), MMP-9 (rs17576, A/G) and TIMP-1 (rs6609533, A/G) SNPs in the pathogenesis of keratoconus.