Role of extracellular matrix remodelling gene SNPs in keratoconus.

: 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.: We genotyped 200 keratoconus and 100 control subjects by allele-specific PCR, and quantified MMP-9 and TIMP1 in tear samples by ELISA.: (rs55703767) and (rs17576) G alleles were over-represented in keratoconus patients (P < 0.01). (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 (rs17576) homozygous (GG) alleles had higher tear MMP-9 compared to those carrying the (A) allele (P < 0.01). Females carrying (rs6609533) homozygous (AA) alleles in both groups had significantly lower tear compared to carriers of the AG and GG genotypes.: This study supports the hypothesis of a functional role for (rs55703767, G/T), (rs17576, A/G) and (rs6609533, A/G) SNPs in the pathogenesis of keratoconus.