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S. Annamaneni, Sr., S. S. H. K. Annamaneni, Sr., Molecular Genetics of Myopia; Role of Col2a1 Gene Polymorphism in the Development of High Myopia. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5941.
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© ARVO (1962-2015); The Authors (2016-present)
Myopia is a most prevalent (about 30%) ocular disorder characterized by refractive error(RE), caused by multiple interacting genetic and environmental factors. Its phenotypic expression can be modulated by qualitative and quantitative variations of different types of collagen and extracellular matrix proteins (EMP's).In high myopia (>10D), reduced ocular accommodation results in retinal defocus, ciliary muscle weakening and defective mechanosensitive transduction pathways. These events in combination with scleral remodeling and accelerated collagen degradation result in diminished collagen fibril architecture, and defective signaling pathway. Col2a1 is one of the important fibrillar collagens for maintenance of vitreous body and sclera. COL2A1 gene mutations have been associated with several syndromes with myopia. Hence, an attempt was made to understand the role of Collagen 2A1 gene polymorphism in etiology of myopia.
Our present study includes160 high myopia cases and 190 age and sex matched controls cases. The Hind III Polymorphism at Intron 33 of COL2A1 gene (12q13.11) and CT dinucleotide ins/del polymorphism at Intron 50 was analysed through PCR followed by RFLP analysis and PAGE respectively. The genotype and allele frequencies were calculated and the comparisons were made with respect to sex of the proband, age at onset, parental consanguinity, familial incidence and RE.
The Hind III site polymorphism of the gene resulted in 3 genotypes on the basis of presence or absence of restriction site, viz. hh genotype (428 bp, 153 bp), Hh genotype (581 bp, 428 bp, 153 bp) and HH genotype (581 bp). Slight elevation of h allele frequency in myopia cases (0.525), in male sex(0.53), in familial cases (0.564), probands with age at onset between 10-20yrs(0.555) and with RE >10D(0.56) was observed. The Intron 50 polymorphism resulted in 3 genotypes,viz L1L1 genotype (594bp), L1L2 genotype (594bp, 592bp) and L2L2 genotype (592bp). The genotype distribution showed slight decrease in L1L1 genotype in disease cases (79%) compared to controls (83.3%). However, there is a significant increase in L1L1 genotype among familial cases of myopia (81.2%), in age at onset group <10yrs (88.3%), and with RE <10D (84%).
Our studies on COL2A1 gene indicate that h allele might confer risk to myopia development while insertion of CT dinucleotide in intronic region of the gene might alter the expression pattern which might predispose individuals to myopia development.
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