The Functional Metabolism and Molecular Biology of Vitamin D Action

Plum, Lori A.; DeLuca, Hector F.

doi:10.1007/s12018-009-9040-z

Cited by 38 publications

(29 citation statements)

References 351 publications

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“…Another problem concerns the measurement of vitamin D levels in the obese patients, because a part of vitamin D is seized in the adipose tissue with lack of an appropriate method of detection in this compartment . Further important confounding factors may affect the vitamin D plasma levels: the sunlight exposition and seasonal variability , a reduced alimentary sources of vitamin D , intestinal malabsorption, lower production of endogenous albumin and reduced hepatic hydroxylation frequent in the cirrhosis . Finally, there is no consensus about the definition of vitamin D deficiency according to plasma measurement: the historical definition is a level of 25(OH)D < 20 ng/mL , but others consider a level < 30 or < 40 ng/mL .…”

Section: Discussionmentioning

confidence: 99%

Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG‐interferon

Boglione

Cusato

Nicolò

et al. 2014

Journal of Viral Hepatitis

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In HBV-infected patients, the vitamin D deficiency has been related to chronic liver diseases, progression of hepatic fibrosis and poor response to the treatment. The CYP27B1 gene, which encodes the 1-α-hidroxylase and involved in the 1,25-dihydroxyvitamin D synthesis, was recently associated to type-1 diabetes, autoimmune disorders and treatment response in HCV. Then, we aimed to investigate the role of CYP27B1 polymorphisms in HBV treatment with PEG-IFN. We retrospectively enrolled 190 patients with chronic hepatitis B HBeAg negative treated for 48 weeks with PEG-IFN α-2a. We examined the role of rs4646536 CYP27B1 SNP (CYP27B1+2838) according to virological and serological response. Our results showed that the TT genotype of CYP27B1+2838 was significantly prevalent in patients with end-of-therapy virological response (37.6%) vs CT/CC (9.4%) (P < 0.001). Virological relapse was prevalent in patients with CT/CC genotype (12.6%) vs TT genotype (2.1%) (P < 0.001). TT genotype was also related to HBsAg loss (P = 0.004) and anti-HBs appearance (P = 0.002). In the multivariate analysis, the TT genotype resulted to be a good positive predictor of sustained virological response (OR = 5.632, IC = 1.938-16.368, P = 0.001) and serological response (OR = 6.161, IC = 1.856-20.457, P = 0.003). The CYP27B1+2838 polymorphism may be useful as pretreatment factor to selection of patients with higher probability of response to therapy.

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Section: Discussionmentioning

confidence: 99%

Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG‐interferon

Boglione

Cusato

Nicolò

et al. 2014

Journal of Viral Hepatitis

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“…The basic metabolism of vitamin D has been extensively reviewed by others e.g. and will therefore not be described here. In brief, vitamin D 3 is primarily acquired endogenously through the photochemical conversion of 7‐dehydrocholesterol to previtamin D 3 in the skin – with sun exposure being paramount to this process.…”

Section: Vitamin D Functions and Metabolismmentioning

confidence: 99%

Vitamin D in chronic liver disease

Stokes

Volmer

Grünhage

et al. 2013

Liver International

151

120

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Chronic liver disease (CLD) and several related extrahepatic manifestations such as hepatic osteodystrophy are associated with deficiency of vitamin D, which has therefore been suggested as therapeutic target. Vitamin D undergoes hepatic 25-hydroxylation, rendering the liver critical to the metabolic activation of this vitamin. Vitamin D deficiency is highly prevalent in CLD patients, and vitamin D levels are inversely related to the severity of CLD. Declining levels of carrier proteins such as albumin and vitamin D-binding protein might also be critical in CLD. Intervention studies report improvements of CLD following supplementation, and benefits to health outcomes in particular with respect to hepatitis C virus infection have recently been documented. Content: We discuss vitamin D sources, functions and metabolism with a focus on the inherent complications of analytical measurements, such as the interference of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D C-3 epimers. Global discrepancies in the definition of optimal serum 25-hydroxyvitamin D levels are covered, and the prevalence of vitamin D deficiency in CLD is reviewed. We also address the functional mechanisms underlying this deficiency, and refer to associations between genetic variation in vitamin D metabolism and CLD. Lastly, we consider the health implications of a vitamin D deficiency in CLD and consider therapeutic options. Summary: Herein, we focus on the epidemiological and functional relationships between vitamin D deficiency and CLD, followed by a discussion of the potential implications for therapeutic interventions.

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“…Esto es debido a que la mayoría de los tejidos corporales tienen receptores para la forma activa de 1,25 dihidroxivitamina D2, conocidos como receptores de la vitamina D (VDR), siendo su gen localizado en el cromosoma 12 (12q13.11). De acuerdo con el estudio de Bray y su equipo, 12 la deficiencia de ésta suele presentar polimorfismo; además, la mayoría de estos tejidos también contienen la enzima CYP27B1, responsable de la conversión de la principal forma circulante de la vitamina D, 25-hidroxivitamina D en su metabolito activo 1,25 dihidroxivitamina D. La regulación de esta conversión a nivel tisular difiere de la activación convencional que se produce en el riñón en que es más dependiente del sustrato y, por lo tanto, más susceptible a la deficiencia de vitamina D. 13 En este estudio llama la atención que en 63% de los casos los niveles séricos de 25-OH vitamina D se encontraran por debajo de los valores aceptados como normales, especialmente en una población socioeconómicamente alta con acceso a una alimentación, a una educación y atención médica mejores que otras poblaciones; otro de los aspectos es que en todos los casos con vitamina D por debajo del rango normal, se encontró una asociación con alguna entidad clínica, desconociendo si ésta es de manera fortuita, casual o causal; sin embargo, la literatura consultada ha brindado explicación científica en la mayoría de los casos de estas asociaciones.…”

Section: Discussionunclassified