title: COL1A1 and COL2A1 genes and myopia susceptibility: evidence of association and suggestive linkage to the COL2A1 locus.
abstract: OBJECTIVE
  Collagen involvement in myopia development via scleral remodeling is well-known. Recently, COL1A1 and COL2A1 gene polymorphisms were reported to be associated with high-grade and common myopia, respectively. This study was conducted to investigate whether these collagen genes are associated and/or genetically linked with myopia in large Caucasian family datasets.
  
  
  METHODS
  High-grade myopia was defined as <or=-5.00 D. Two independent datasets comprising 146 (Duke) and 130 (Cardiff) families with high-grade myopia participated in the association study. Allelic discrimination assays were performed on tagging SNPs for COL1A1 and COL2A1. The pedigree disequilibrium test (PDT) and the association test in the presence of linkage (APL) were used for association analyses. Linkage analyses for COL2A1 locus markers were performed with the Fastlink and Merlin programs in conjunction with data obtained from our collaborative whole-genome linkage study (254 families).
  
  
  RESULTS
  Significant association was identified between five SNPs (rs1034762, rs1635529, rs1793933, rs3803183, and rs17122571) of the COL2A1 locus and high-grade myopia (P < 0.045, minimum (min) P = 0.008) and with myopia status set at <or=-0.50 or -0.75 D (min P = 0.004) in the Duke dataset. The SNP rs1635529 also showed significant association in the Cardiff dataset (<or=-5.00 D, min P = 0.004; <or=-0.50 D, min P = 0.007). Linkage analyses showed suggestive linkage to the COL2A1 locus on 12q. No association was found between COL1A1 SNPs and any degree of myopia.
  
  
  CONCLUSIONS
  The COL2A1 gene was associated with high-grade myopia in two independent Caucasian family datasets. COL1A1 gene polymorphisms were not associated with myopia in our dataset, indicating possible heterogeneity across different ethnicities.
authors.affiliation: Center for Human Genetics, North Carolina, USA.
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Metlapally
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Khanh-Nhat
authors.initials: KN
authors.lastname: Tran-Viet
authors.forename: Diana
authors.initials: D
authors.lastname: Abbott
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Czaja
authors.forename: Francois
authors.initials: F
authors.lastname: Malecaze
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.forename: David
authors.initials: D
authors.lastname: Mackey
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Sandrine
authors.initials: S
authors.lastname: Paget
authors.forename: Tetyana
authors.initials: T
authors.lastname: Zayats
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D000328:Adult; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C499177:COL2A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II; D005819:Genetic Markers