Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration

Intervertebral disk degeneration （IDD） is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential asso- ciation between IDD and FokI polymorphism located in the gene encoding the vitamin D receptor （VDR）, and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the FokI polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from PubMed, EMBASE, China National Knowledge Infrastructure （CNKI）, and China Biology Medical （CBM） with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozy- gore, heterozygote, dominant, and recessive models revealed no significant correlation between the FokI polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associ- ations were detected for Hispanics based on allele contrast （OR = 1.395, 95% CI = 1.059-1.836, P = 0.018）, homozygote （OR = 1.849, 95% CI = 1.001-3.416, P = 0.049）, heterozygote （OR = 1.254, 95% CI = 1.049-1.498, P = 0.013）, and dominant （OR = 1.742, 95% CI = 1.174-2.583, P = 0.006） models, and for Asians using the dominant model （OR = 1.293, 95% CI = 1.025-1.632, P --- 0.030）, whereas there is no significant association detected for Caucasians. In conclusion, FokI polymorpbism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying FokI allele T.

Immunohistochemical evaluation of vitamin D receptor(VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

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-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-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 Fok I,"B"and"b"for Bsm I,"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% positive vs.<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.