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Vitamin D receptor (VDR) and group-specific component (GC, vitamin D-binding protein) polymorphisms in myopia.

ABSTRACT: Epidemiologic evidence indicates that time outdoors reduces the risk of myopia, suggesting a possible role for vitamin D. This case-control study was conducted to determine whether single-nucleotide polymorphisms (SNPs) within VDR at 12q13.11 and GC at 4q12-13 are associated with myopia.The primary analysis was conducted on 81 white adult control subjects between 18 and 50 years of age with a spherical equivalent refractive error between +0.50 and +2.00 D in both eyes and less than 1.50 D of astigmatism. Affected myopic subjects were 289 unrelated white adults at least 18 years of age with at least -0.75 D myopia in both principal meridians of both eyes.One SNP within VDR was significantly associated with myopia in the multivariate analysis of the primary sample (rs2853559: odds ratio = 1.99, P = 0.003). In a subsample of less severely myopic white subjects between -0.75 and -4.00 D, three SNPs within VDR were significantly associated in a multivariate model after adjustment for multiple comparisons (rs2239182: odds ratio = 2.17, P = 0.007; rs3819545: odds ratio = 2.34, P = 0.003; rs2853559: odds ratio = 2.14, P = 0.0035), accounting for 12% of model variance over age alone.Polymorphisms within VDR appear to be associated with low to moderate amounts of myopia in white subjects. Future studies should determine whether this finding can be replicated and should explore the biological significance of these variations with respect to myopia.

SUBMITTER: Mutti DO

PROVIDER: S-EPMC3109057 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Vitamin D receptor (VDR) and group-specific component (GC, vitamin D-binding protein) polymorphisms in myopia.

Mutti Donald O DO Cooper Margaret E ME Dragan Ecaterina E Jones-Jordan Lisa A LA Bailey Melissa D MD Marazita Mary L ML Murray Jeffrey C JC Zadnik Karla K

Investigative ophthalmology & visual science 20110601 6

<h4>Purpose</h4>Epidemiologic evidence indicates that time outdoors reduces the risk of myopia, suggesting a possible role for vitamin D. This case-control study was conducted to determine whether single-nucleotide polymorphisms (SNPs) within VDR at 12q13.11 and GC at 4q12-13 are associated with myopia.<h4>Methods</h4>The primary analysis was conducted on 81 white adult control subjects between 18 and 50 years of age with a spherical equivalent refractive error between +0.50 and +2.00 D in both ...[more]

PMID: 21357399

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Project description:BackgroundVitamin D-binding protein or group-specific component (Gc) is the major plasma carrier protein of Vitamin D. Two single nucleotide polymorphisms, rs7041 (NM_000583.3:c.1296G>T;NP_000574.2:p.Asp432Glu) and rs4588 (c.1307C>A; p.Thr436Lys), in the GC gene result in three major genotypes, that is, GC1F (c.1296T, c.1307C), GC1S (c.1296G, c.1307C), GC2 (c.1296T, c.1307A), and phenotypes such as Gc1F (p.432Asp, p.436Thr), Gc1S (p.432Glu, p.436Thr), and Gc2 (p.432Asp, p.436Lys). Significant variations in the frequencies of GC subtypes (genotypes/phenotypes) are reported in different populations living in different geographical locations, for example, GC1S/Gc1S (c.1296G, c.1307C/p.432Glu, p.436Thr) and GC2/Gc2 (c.1296T, c.1307A/p.432Asp, p.436Lys) are predominant in Caucasians and people living in the northern hemisphere, and GC1F/Gc1F (c.1296T, c.1307C/p.432Asp, p.436Thr) is predominant in Africans. However, frequencies of major GC subtypes are not known in the Kuwaiti population. In this study, we investigated 512 alleles to identify the major GC subtypes in Kuwaiti nationals.MethodsGenomic DNA was isolated from blood samples of 128 healthy subjects. DNA regions covering the targeted mutations were amplified by PCR. Amplified DNAs were sequenced by the Sanger method and analyzed for specific mutations to determine the GC genotypes and phenotypes.ResultsThe results identified the presence of four GC genotypes/phenotypes namely GC1F/Gc1F (c.1296T, c.1307C/p.432Asp, p.436Thr), GC1S/Gc1S (c.1296G, c.1307C/p.432Glu, p.436Thr), GC2/Gc2 (c.1296T, c.1307A/p.432Asp, p.436Lys), and GC3/Gc3 (c.1296G;c.1307A/p.432Glu, p.436Lys). Among the allelic subtypes (n = 512), GC1S (c.1296G; c.1307C) (n = 270, 52.7%) was predominant, followed by GC1F (c.1296T; c.1307C) (n = 138, 27%), GC2 (c.1296T; c.1307A) (n = 72, 14%), and GC3 (c.1296G; c.1307A) (n = 32, 6.3%). Three common subtypes, that is, GC1F (c.1296T; c.1307C), GC1S (c.1296G; c.1307C), and GC2 (c.1296T; c.1307A) are well documented in the literature, but GC3 (c.1296T; c.1307A) is an uncommon variant found in our study subjects.ConclusionWe found that GC subtype distribution was unique in the Kuwaiti population, with some affinity to Caucasians. Several factors including ancestral origin, migration history, and environmental forces such as solar intensity may be responsible for the unique distribution of GC subtypes in this population.

Project description:Objective: Vitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms.Methods: We evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T),VDR-BsmI-rs1544410 (G>A),VDR-ApaI-rs7975232 (T>G), andVDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism). Absence or presence of restriction site was denoted by a capital or lower letter, respectively: " F" and " f" for FokI, " B" and " b" for BsmI, " A" and " a" for ApaI, and " T" and " t" for TaqI endonuclease. Seventy-four Italian cutaneous primary melanomas (52.1±12.7 years old) were studied; 51.4% were stage I, 21.6% stage II, 13.5% stage III, and 13.5% stage IV melanomas. VDR expression was categorized as follows: 100% positivevs. <100%; over the median 20% (high VDR expression) vs. ≤20% (low VDR expression); absence vs. presence of VDR-expressing cells.Results: Stage I melanomas, Breslow thickness of <1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT combined genotype were more frequent in melanomas with high vs. low VDR expression. Combined genotypes BbAA, bbAa, AATt, BbAATt, and bbAaTT were more frequent in 100% vs. <100% VDR-expressing cells. Combined genotype AATT was more frequent in melanomas lacking VDR expression (odds ratio=14.5; P=0.025). VDR expression was not associated with metastasis, ulceration, mitosis >1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional skin and non-skin cancers, and melanoma familiarity.Conclusions: We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells. Low VDR expression in AATT carriers is a new finding that merits further study. VDR expression possibly poses implications for vitamin D supplementation against melanoma. VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.

Dataset Information

Vitamin D receptor (VDR) and group-specific component (GC, vitamin D-binding protein) polymorphisms in myopia.

Publications

Vitamin D receptor (VDR) and group-specific component (GC, vitamin D-binding protein) polymorphisms in myopia.

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