title: AC and AG dinucleotide repeats in the PAX6 P1 promoter are associated with high myopia.
abstract: OBJECTIVE
  The PAX6 gene, located at the reported myopia locus MYP7 on chromosome 11p13, was postulated to be associated with myopia development. This study investigated the association of PAX6 with high myopia in 379 high myopia patients and 349 controls.
  
  
  METHODS
  High myopia patients had refractive errors of -6.00 diopters or greater and axial length longer than 26 mm. Control subjects had refractive errors less than -1.00 diopter and axial length shorter than 24 mm. The P1 promoter, all coding sequences, and adjacent splice-site regions of the PAX6 gene were screened in all study subjects by polymerase chain reaction and direct sequencing. PAX6 P1 promoter-luciferase constructs with variable AC and AG repeat lengths were prepared and transfected into human ARPE-19 cells prior to assaying for their transcriptional activities.
  
  
  RESULTS
  No sequence alterations in the coding or splicing regions showed an association with high myopia. Two dinucleotide repeats, (AC)(m) and (AG)(n), in the P1 promoter region were found to be highly polymorphic and significantly associated with high myopia. Higher repeat numbers were observed in high myopia patients for both (AC)(m) (empirical p = 0.013) and (AG)(n) (empirical p = 0.012) dinucleotide polymorphisms, with a 1.327-fold increased risk associated with the (AG)(n) repeat (empirical p = 0.016; 95% confidence interval: 1.059-1.663). Luciferase-reporter analysis showed elevated transcription activity with increasing individual (AC)(m) and (AG)(n) and combined (AC)(m)(AG)(n) repeat lengths.
  
  
  CONCLUSIONS
  Our results revealed an association between high myopia and AC and AG dinucleotide repeat lengths in the PAX6 P1 promoter, indicating the involvement of PAX6 in the pathogenesis of high myopia.
authors.affiliation: Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong S.A.R.
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Ng
authors.forename: Ching Yan
authors.initials: CY
authors.lastname: Lam
authors.forename: Dennis Shun Chiu
authors.initials: DS
authors.lastname: Lam
authors.forename: Sylvia Wai Yee
authors.initials: SW
authors.lastname: Chiang
authors.forename: Pancy Oi Sin
authors.initials: PO
authors.lastname: Tam
authors.forename: Dan Yi
authors.initials: DY
authors.lastname: Wang
authors.forename: Bao Jian
authors.initials: BJ
authors.lastname: Fan
authors.forename: Gary Hin-Fai
authors.initials: GH
authors.lastname: Yam
authors.forename: Dorothy Shu Ping
authors.initials: DS
authors.lastname: Fan
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D018900:Dinucleotide Repeats / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009216:Myopia / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors