Received 20 November 2008; received in revised form 25 February 2009; accepted 26 February 2009. published online 04 June 2009.
Objective
To assess whether genetic variation in cMET is associated with refractive error or change in refractive error over time.
Design
Cohort study.
Participants and Controls
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.
Main Outcome Measures
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; χ2 for trend P = 0.014) (Schools 2 and 3; χ2 for trend = 5.42, P = 0.020) (combined N = 1126, overall χ2 for trend = 10.90, P = 9.6×10−4). 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) (PSet1 = 0.004, PSet2 = 0.02, Combined N = 559, P = 3.0×10−4).
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.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Available online: June 4, 2009.
1Genetic Medicine Group, Singapore Institute for Clinical Sciences, Singapore
2Immunity and Inflammation Group, the Wellcome Trust Center for Human Genetics, University of Oxford, United Kingdom
3Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
4Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
6Department of Paediatrics, National University Hospital, and School of Medicine, National University of Singapore, Singapore
7NUS-GIS Centre for Molecular Epidemiology, National University of Singapore, Singapore
Correspondence: Chiea C. Khor, MBBS, DPhil, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609
Manuscript no. 2008-1378.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Funding for this study was provided by the National Medical Research Council (NMRC/0975/2005), Biomedical Research Council (BMRC 06/1/21/19/466) of the Agency for Science, Technology and Research (A-STAR), and the Centre for Molecular Epidemiology, National University of Singapore. CCK and RTG are scholars of A-STAR.
ABSTRACT