cMET and refractive error progression in children.
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.
Khor
Chiea C
CC
Genetic Medicine Group, Singapore Institute for Clinical Sciences, Singapore. khor_chiea_chuen@sics.a-star.edu.sg
Grignani
Robert
R
Ng
Daniel P K
DP
Toh
Kai Yee
KY
Chia
Kee-Seng
KS
Tan
Donald
D
Goh
Denise L M
DL
Saw
Seang-Mei
SM
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
D005819:Genetic Markers; D019859:Proto-Oncogene Proteins c-met