title: Correlation between the COL4A3, MMP-9, and TIMP-1 polymorphisms and risk of keratoconus.
abstract: OBJECTIVE
  Keratoconus (KC) is thinning of the central cornea. Its etiology is unknown, but it may result from degrading of collagen type IV. The major protein in the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9 enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1 (TIMP-1). In the present study, we sought to investigate and evaluate the effects of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC in an Iranian population sample.
  
  
  METHODS
  This case-control study was performed on 140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification refractory mutation system polymerase chain reaction (ARMS-PCR).
  
  
  RESULTS
  Our findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR = 0.26, 95% CI = 0.08-0.82, P = 0.022). rs17576A/G, associated with KC and the A allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06-4.76, P = 0.036). In males, the allele frequency was not associated with KC risk/protection.
  
  
  CONCLUSIONS
  This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.
authors.affiliation: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.|Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Saravani
authors.affiliation: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. Davidyari.85@gmail.com.|Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Davidyari.85@gmail.com.
authors.forename: Davood
authors.initials: D
authors.lastname: Yari
authors.affiliation: Department of Molecular Genetics, University of Zabol, Zabol, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Saravani
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Hasanian-Langroudi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002648:Child; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism; D003315:Cornea / Q000201:enzymology* / Q000473:pathology; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007492:Iran / Q000453:epidemiology; D007640:Keratoconus / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D019715:Tissue Inhibitor of Metalloproteinase-1; C057112:type IV collagen alpha3 chain; D004247:DNA; D020780:Matrix Metalloproteinase 9
keywords: COL4A3; Keratoconus; MMP-9; Polymorphism; TIMP-1