title: cMET and refractive error progression in children.
abstract: OBJECTIVE
  To assess whether genetic variation in cMET is associated with refractive error or change in refractive error over time.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Discovery set (Set 1: N = 579 children; 403 cases, 176 controls). Confirmatory set (Set 2: N = 547 children; 338 cases, 209 controls).
  
  
  METHODS
  Children in the discovery set were genotyped for a panel of genetic markers within cMET. Markers that were found to be significantly associated with the presence of refractive error or more rapid change in refractive error were then genotyped in the confirmatory set.
  
  
  METHODS
  Presence or absence of myopia and the rate of change in refractive error over a 3-year follow-up period.
  
  
  RESULTS
  Carriage of the variant cMET +110703 A allele was found to associate with increased susceptibility to myopia. The variant was also found to associate with a faster rate of change in refractive error in both the discovery set and the confirmatory cohort regardless of the initial refractory ability (School 1; chi(2) for trend P = 0.014) (Schools 2 and 3; chi(2) for trend = 5.42, P = 0.020) (combined N = 1126, overall chi(2) for trend = 10.90, P = 9.6 x 10(-4)). Carriage of the variant allele was also found to be significantly overrepresented in children within the fastest changing quartile (Q4: mean change of -3.01 D over 3 years) compared with the slowest (Q1: mean change of -0.28 D over 3 years) (P(Set1) = 0.004, P(Set2) = 0.02, Combined N = 559, P = 3.0 x 10(-4)).
  
  
  CONCLUSIONS
  Our data implicate the involvement of cMET in the pathogenesis of myopia in general, as well as more rapid progression in refractive error regardless of the initial refractory ability. These results underline the importance of eye growth genes in the development of common myopia.
authors.affiliation: Genetic Medicine Group, Singapore Institute for Clinical Sciences, Singapore. khor_chiea_chuen@sics.a-star.edu.sg
authors.forename: Chiea C
authors.initials: CC
authors.lastname: Khor
authors.forename: Robert
authors.initials: R
authors.lastname: Grignani
authors.forename: Daniel P K
authors.initials: DP
authors.lastname: Ng
authors.forename: Kai Yee
authors.initials: KY
authors.lastname: Toh
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Donald
authors.initials: D
authors.lastname: Tan
authors.forename: Denise L M
authors.initials: DL
authors.lastname: Goh
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
mesh_terms: D002648:Child; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D012029:Refraction, Ocular; D012030:Refractive Errors / Q000235:genetics* / Q000503:physiopathology*; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D019859:Proto-Oncogene Proteins c-met