title: Systematic investigation of the relationship between high myopia and polymorphisms of the MMP2, TIMP2, and TIMP3 genes by a DNA pooling approach.
abstract: OBJECTIVE
  This study examined the relationship between high myopia and three myopia candidate genes--matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase-2 and -3 (TIMP2 and TIMP3)--involved in scleral remodeling.
  
  
  METHODS
  Recruited for the study were unrelated adult Han Chinese who were high myopes (spherical equivalent, ≤ -6.0 D in both eyes; cases) and emmetropes (within ±1.0 D in both eyes; controls). Sample set 1 had 300 cases and 300 controls, and sample set 2 had 356 cases and 354 controls. Forty-nine tag single-nucleotide polymorphisms (SNPs) were selected from these candidate genes. The first stage was an initial screen of six case pools and six control pools constructed from sample set 1, each pool consisting of 50 distinct subjects of the same affection status. In the second stage, positive SNPs from the first stage were confirmed by genotyping individual samples forming the DNA pools. In the third stage, positive SNPs from stage 2 were replicated, with sample set 2 genotyped individually.
  
  
  RESULTS
  Of the 49 SNPs screened by DNA pooling, three passed the lenient threshold of P < 0.10 (nested ANOVA) and were followed up by individual genotyping. Of the three SNPs genotyped, two TIMP3 SNPs were found to be significantly associated with high myopia by single-marker or haplotype analysis. However, the initial positive results could not be replicated by sample set 2.
  
  
  CONCLUSIONS
  MMP2, TIPM2, and TIMP3 genes were not associated with high myopia in this Chinese sample and hence are unlikely to play a major role in the genetic susceptibility to high myopia.
authors.affiliation: Department of Health Technology and Informatics, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China.
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Leung
authors.forename: Wai Chi
authors.initials: WC
authors.lastname: Yiu
authors.forename: Maurice K H
authors.initials: MK
authors.lastname: Yap
authors.forename: Po Wah
authors.initials: PW
authors.lastname: Ng
authors.forename: Wai Yan
authors.initials: WY
authors.lastname: Fung
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Shea Ping
authors.initials: SP
authors.lastname: Yip
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D047728:Myopia, Degenerative / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012590:Sclera / Q000502:physiology; D017422:Sequence Analysis, DNA / Q000379:methods*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D055815:Young Adult
chemical_list: C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2