DHCR7: A vital enzyme switch between cholesterol and vitamin D production

Prabhu, Anika V.; Luu, Winnie; Li, Dianfan; Sharpe, Laura J.; Brown, Andrew

doi:10.1016/j.plipres.2016.09.003

Cited by 132 publications

(92 citation statements)

References 159 publications

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“…The DHCR7 gene encodes 7-dehydrocholesterol reductase, an enzyme involved in the final step of cholesterol synthesis [37]. The SNP, rs12785878, located near the DHCR7 gene on chromosome 11q12, has been linked to vitamin D serum concentrations in several studies [22, 27].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients

et al. 2017

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BackgroundPatients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection.MethodsThe study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis.ResultsSVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0–1 (OR = 5.00; 95% CI, 2.02–12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03–7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13–3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection.ConclusionThe DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0613-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients

et al. 2017

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“…Cholesterol and vitamin D (but not 1,25(OH) 2 D) increase proteasomal degradation of DHCR7, as does UVB, leading to increased vitamin D production . AMPK, a key sensor and regulator of cellular energy homeostasis, and protein kinase A are potent inhibitors of DHCR7, whereas CaMKII has a lower inhibitory effect . Most textbooks and reviews clearly state that the photochemical production of vitamin D in the skin is a nonenzymatic reaction.…”

Section: ‐Dehydrocholesterol Reductase (Dhcr7)mentioning

confidence: 99%

“…(30) AMPK, a key sensor and regulator of cellular energy homeostasis, and protein kinase A are potent inhibitors of DHCR7, whereas CaMKII has a lower inhibitory effect. (31,32) Most textbooks and reviews clearly state that the photochemical production of vitamin D in the skin is a nonenzymatic reaction. Although this remains technically correct, recent data suggest that the activity of DHCR7 is under (cellular) metabolic and genetic control.…”

Section: -Dehydrocholesterol Reductase (Dhcr7)mentioning

confidence: 99%

Vitamin D Metabolism Revised: Fall of Dogmas

Bouillon

Bikle

2019

Journal of Bone and Mineral Research

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“…This is exemplified by a number of inherited disorders, such as the SmithLemli-Opitz syndrome (SLOS; see Fig. 2(c)), the molecular etiology of which lies in subtle defects in cholesterol biosynthesis [3,35,40,42]. SLOS is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis.…”

Section: Molecular Idiosyncrasies Of Cholesterol: Key To Functionalitymentioning

confidence: 99%

Cholesterol: An evergreen molecule in biology

Kumar

Chattopadhyay

2016

BSI

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Abstract. Cholesterol, an essential component of higher eukaryotic membranes, was discovered more than two centuries ago. The development and progress of cholesterol research in the last 200 years has been truly fascinating, with elements of surprise, serendipity and intrigue. In this review, we trace this journey the way we see it, and follow it up with the role of membrane cholesterol in crucial areas of contemporary research (transbilayer domains, regulation of GPCR function and role in the entry of intracellular pathogens into host cells), with considerable footprint from our work. We believe that cholesterol will continue to surprise and fascinate future researchers, thereby justifying its evergreen nature. Keywords: Membrane cholesterol, transbilayer dimer, G protein-coupled receptor, pathogen entry Abbreviations 7-DHC7-dehydrocholesterol 7-DHCR 3β-hydroxy-steroid-7 -reductase 25-NBD-cholesterol 25-[N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-methyl]amino]-27-norcholesterol CRAC cholesterol recognition/interaction amino acid consensus DHE dehydroergosterol ( 5,7,9(11)22 -ergostatetraen-3β-ol) DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine FRAP fluorescence recovery after photobleaching GPCR G protein-coupled receptor NBD 7-nitrobenz-2-oxa-1,3-diazol-4-yl REES red edge excitation shift SLOS Smith-Lemli-Opitz syndrome

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DHCR7: A vital enzyme switch between cholesterol and vitamin D production

Cited by 132 publications

References 159 publications

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients

Vitamin D Metabolism Revised: Fall of Dogmas

Cholesterol: An evergreen molecule in biology

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