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Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.

ABSTRACT: Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1? and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1? levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis.

SUBMITTER: Triantos C

PROVIDER: S-EPMC6138740 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.

Triantos Christos C Aggeletopoulou Ioanna I Kalafateli Maria M Spantidea Panagiota I PI Vourli Georgia G Diamantopoulou Georgia G Tapratzi Dimitra D Michalaki Marina M Manolakopoulos Spilios S Gogos Charalambos C Kyriazopoulou Venetsana V Mouzaki Athanasia A Thomopoulos Konstantinos K

Scientific reports 20180914 1

Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring ...[more]

PMID: 30218108

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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

Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.

Publications

Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.

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