Association of vitamin D receptor gene start codon (Fok1) polymorphism with high myopia

Abstract

Background:High myopia caused primarily due to abnormal emmetropization and excessive axial ocular elongation is associated with sight-threatening ocular pathology. Muscular dysfunction of ocular ciliary muscles due to altered intracellular calcium levels can result in defective mechanotransduction of the eye and retinal defocus. The vitamin D3 receptor (VDR; a intracellular hormone receptor) is known to mediate calcium homeostasis, influencing the development of myopia.Materials and Methods:In the present study, a total of 206 high myopia, 98 low myopia and 250 control samples were analyzed for VDR gene Fok1 (exon 2 start codon) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.Results:High myopia patients revealed decrease in the frequency of ff homozygotes (8.3%) as compared to control group (14.0%), with a corresponding increase in frequency of FF homozygotes (68.9% in high myopia vs. 62.8% in controls). The frequency of f allele carriers (Ff and ff) was increased in females of high myopia (35.6%) and low myopia cases (45.4%). Elevated frequency of f allele was found only in early age at onset cases of high myopia (0.227) and later age at onset (10–20 years) cases of low myopia (0.273) as well as in low myopia cases with parental consanguinity (0.458) (P 0.035; χ2 = 6.692*).Conclusion:The results suggest that VDR gene might not be playing a direct role in the development of myopia, but might contribute indirectly to the risk conferred by mechanical stress factors or growth/development related factors through its role in calcium homeostasis and regulation of ciliary muscle function.

Serum 25-hydroxyvitamin D level is associated with myopia in the Korea national health and nutrition examination survey

“…One hypothesis posits that lower 25(OH)D levels induce alterations in intracellular calcium and impaired contraction and relaxation of the ciliary muscles, thereby leading to myopia development. [61,62] Another hypothesis is that 25(OH)D may be involved in a retinoscleral signaling pathway. [63] Retinoic acid is known to be a factor in the retinoscleral signal for eyeball lengthening.…”

“…[79–80] Some studies found in receptor polymorphism of 1,25(OH)D in myopic population. [61,81] But it is still unclear that how 1,25 (OH)D affects myopic progression. [82] …”

Association of vitamin D receptor gene polymorphisms with polycystic ovary syndrome among Indian women

“…The VDR gene is mapped to chromosomal locus 12q12-14 comprising pre-extensive promoter region and capable of generating multiple tissue-specific transcripts. Several VDR polymorphisms have been investigated for functional significance and potential effects on disease susceptibility to complex diseases such as osteoarthritis (OA), diabetes, cancer, high myopia, cardiovascular disease and tuberculosis 16 17 18 19 20 21 . A few studies have also been focussed on association of VDR gene in endocrine disorders including PCOS 22 23 24 .…”

Vitamin D: Implications for ocular disease and therapeutic potential

“…In a subgroup of myopes from this study (between −0.75 and −4.00 D), three SNPs in the VDR were identified that were significantly linked to myopia (Mutti et al, 2011). The Fok1 VDR polymorphism, however, which has been found to affect calcium homeostasis (Gross et al, 1996; Jurutka et al, 2001), was not found to confer risk for either high or low myopia, although the frequency of the f allele was higher in females, particularly in those subjects with low myopia (Annamaneni et al, 2011). …”

“…Several studies have examined variations in the VDR as potential risk factors for myopia development. The VDR gene is located near loci identified to be associated with myopia (MYP-3) (Annamaneni et al, 2011). In addition, deregulated calcium homeostasis has been implicated in ciliary muscle dysfunction, leading to problems with emmetropization and mechanical stress (Dulhunty et al, 2006).…”