scholarly journals Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1954 ◽  
Author(s):  
Veronika Fedirko ◽  
Hannah Mandle ◽  
Wanzhe Zhu ◽  
David Hughes ◽  
Afshan Siddiq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Multiple Testing ◽  
A Priori ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Vitamin D Metabolism ◽  
Gene Pathway ◽  
Vitamin D Levels ◽  
Large Populations

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

scholarly journals Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis

2009 ◽  
Vol 16 (2) ◽  
pp. 133-138 ◽  
Author(s):  
K. Claire Simon ◽  
Kassandra L Munger ◽  
Xing Yang ◽  
Alberto Ascherio
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Conditional Logistic Regression ◽  
Dietary Vitamin ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Metabolism ◽  
Logistic Regression Models ◽  
Gene Environment ◽  
Vitamin D Levels

The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls. Conditional logistic regression models were used to calculate relative risks (RR) and 95% confidence intervals (CIs) and to assess the significance of gene—environment interactions. No associations were observed for any of the single-nucleotide polymorphisms (SNPs) in VDR, CYP27B1, CYP24A1, CYP2R1 or DBP (p > 0.05 for all). The authors did observe an interaction (p = 0.04) between dietary intake of vitamin D and the vitamin D receptor FokI polymorphism on MS risk. The protective effect of increasing vitamin D was evident only in individuals with the ‘ff ’ genotype (RR = 0.2, 95% CI: 0.06, 0.78; p = 0.02 for 400 IU/day increase). It was concluded that this does not support a role for the selected SNPs involved in vitamin D metabolism in the etiology of MS. The finding of a marginally significant gene—environment interaction requires replication in larger datasets, but suggests future genetic studies may benefit from considering relevant environmental context.

Contribution of CYP27B1 and CYP24A1 genetic variations to the incidence of acute coronary syndrome and to vitamin D serum level

2019 ◽  
Vol 97 (12) ◽  
pp. 1152-1158 ◽  
Author(s):  
Marina Sherif Fam ◽  
Sally I. Hassanein ◽  
Mohamed Farouk Abdel Rahman ◽  
Reem Amr Assal ◽  
Rasha Sayed Hanafi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Acute Coronary Syndrome ◽  
Ultra Performance Liquid Chromatography ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Metabolism ◽  
Public Health Burden ◽  
Hydroxyvitamin D ◽  
Coronary Syndrome ◽  
Vitamin D Levels

Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR–RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence.

scholarly journals Vitamin D and Rehabilitation after Stroke: Status of Art

2020 ◽  
Vol 10 (6) ◽  
pp. 1973 ◽  
Author(s):  
Mariacristina Siotto ◽  
Massimo Santoro ◽  
Irene Aprile
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Stroke Recovery ◽  
Stroke Severity ◽  
Nucleotide Polymorphisms ◽  
Stroke Patients ◽  
Vitamin D Metabolism ◽  
Rehabilitation Treatment ◽  
Post Stroke ◽  
Vitamin D Levels

Stroke is the first cause of disability in the population and post-stroke patients admitted to rehabilitation units often present a malnutrition status which can influence nutritional indices and then vitamin levels. Vitamin D deficiency seems implicated beyond stroke severity and stroke risk, and also affects post-stroke recovery. Some studies on vitamin D levels and outcome in stroke patients are available but very few data on vitamin D levels and outcome after rehabilitation treatment are reported. This literature review shows the possible relationship between vitamin D deficiency and recovery in post-stroke patients undergoing rehabilitation treatment. Moreover, because several studies have reported that single nucleotide polymorphisms and promoter methylation in genes are involved in vitamin D metabolism and might affect circulating vitamin D levels, these aspects are evaluated in the current paper. From the studies evaluated in this review, it emerges that vitamin D deficiency could not only have an important role in the recovery of patients undergoing rehabilitation after a stroke, but that genetic and epigenetic factors related to vitamin D levels could have a crucial role on the rehabilitation outcome of patients after stroke. Therefore, further studies are necessary on stroke patients undergoing rehabilitation treatment, including: (a) the measurement of the 25(OH) vitamin D serum concentrations at admission and post rehabilitation treatment; (b) the identification of the presence/absence of CYP2R1, CYP27B1, CYP24A1 and VDR polymorphisms, and (c) analysis of the methylation levels of these genes pre- and post-rehabilitation treatment.

scholarly journals Vitamin D Receptor Gene Polymorphisms Have Negligible Effect on Human Height

2008 ◽  
Vol 11 (5) ◽  
pp. 488-494 ◽  
Author(s):  
Stuart Macgregor ◽  
Jouke-Jan Hottenga ◽  
Penelope A. Lind ◽  
H. Eka D. Suchiman ◽  
Gonneke Willemsen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Multiple Testing ◽  
Meta Analysis ◽  
Receptor Gene ◽  
Phenotypic Variance ◽  
Multiple Testing Correction ◽  
Vdr Gene ◽  
Vitamin D Levels ◽  
Human Height

AbstractHuman height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N= 3906) and the Netherlands (N= 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains ~0.1% of the phenotypic variance in height — this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height.

scholarly journals Association of CYP27B1 Polymorphism and Vitamin D Levels with Multiple Sclerosis Development in Lebanese Population of Bekaa Region: A Preliminary Study

2021 ◽  
Vol 5 (1) ◽  
pp. 18
Author(s):  
Sumaia Braidy ◽  
Alaa Maan Matar ◽  
Jamilah Borjac
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Environmental Factors ◽  
Vitamin D Deficiency ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels ◽  
And Gender ◽  
Cytochrome P450 Family

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Interaction between genetic and environmental factors guides the development of the disease. Among environmental factors, vitamin D deficiency is shown to increase the risk of MS development. Several single nucleotide polymorphisms (SNPs) in cytochrome P450 family 27 subfamily B (CYP27B1) gene that encodes the rate-limiting enzyme involved in vitamin D metabolism, were shown to be correlated with MS. We aimed at investigating the association of CYP27B1 gene polymorphisms and vitamin D level with MS development in a sample of Lebanese MS patients living in the Bekaa region. Enrolled MS patients and controls were age and gender matched. Genotyping was performed by sequencing the amplified CYP27B1 PCR products. Vitamin D levels were measured using a VIDAS® 25 OH Vitamin D total assay based on enzyme linked fluorescent assay (ELFA). Chi-square and Mann-Whitney U tests were used for statistical analysis. A significant association was shown between vitamin D deficiency and MS without any association between CYP27B1 studied SNPs and the disease. We confirmed that vitamin D deficiency was associated with MS with no implication of the studied SNPs of CYP27B1 gene with disease susceptibility among the Lebanese MS patients living in the Bekaa region.

scholarly journals Genetic Polymorphisms of Vitamin D Metabolism Genes and Serum Level of Vitamin D in Colorectal Cancer

2017 ◽  
Vol 32 (4) ◽  
pp. 441-446 ◽  
Author(s):  
Veronica Marques Vidigal ◽  
Pedro Nazareth Aguiar ◽  
Tiago Donizetti Silva ◽  
Juliana de Oliveira ◽  
Célia Aparecida Marques Pimenta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Active Form ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Active Vitamin ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Active Vitamin D ◽  
Vitamin D Levels

Background The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D3 (circulating form) and 1,25(OH)2D3 (active form), in colorectal cancer (CRC) patients. Methods One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. Results The median serum levels of circulating vitamin D were not different between CRC patients and controls; however, the percentage of those with deficient vitamin D was higher in patients with cancer. The active form of the vitamin D was higher in CRC patients. VDR, CYP27B1 and CYP24A1 polymorphic genotypes had no influence on serum levels of circulating vitamin D. The correlation between circulating and active vitamin D forms was lower among patients with CRC, regardless of the presence or absence of any genetic polymorphism. The mean serum levels of active vitamin D were higher among patients with polymorphic genotype variants of Apa1 or Bsm1. Conclusions CRC patients had a higher frequence of insufficient vitamin D and a higher concentration of active vitamin D. These concentration were higher between patients with polymorphic genotypes variants of ApaI and BsmI, CYP24A1 and CYP27B1. Polymorphic genotypes cause a lower correlation between the forms of vitamin D.

scholarly journals DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
María Ángeles JIMÉNEZ-SOUSA ◽  
José Luis JIMÉNEZ ◽  
Amanda FERNÁNDEZ-RODRÍGUEZ ◽  
José María BELLÓN ◽  
Carmen RODRÍGUEZ ◽  
...  
Keyword(s):  
Vitamin D ◽  
Retrospective Study ◽  
Multiple Testing ◽  
Linear Models ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Hiv Diagnosis ◽  
Aids Progression ◽  
Inheritance Model ◽  
The Moment

Abstract Background Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients. Methods We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience’s MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). Results All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). Conclusions DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.

scholarly journals Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Mezawa ◽  
Tsutomu Sugiura ◽  
Michiaki Watanabe ◽  
Chihiro Norizoe ◽  
Daisuke Takahashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Serum Vitamin ◽  
Post Hoc Analysis ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Post Hoc

scholarly journals NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 528
Author(s):  
Shu-Pin Huang ◽  
Yei-Tsung Chen ◽  
Lih-Chyang Chen ◽  
Cheng-Hsueh Lee ◽  
Chao-Yuan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Tyrosine Kinases ◽  
Multiple Testing ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Cancer Specific Survival

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

scholarly journals Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of Cholecalciferol Treatment

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3873
Author(s):  
Alexandra Povaliaeva ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Viktor Bogdanov ◽  
Larisa Dzeranova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Controlled Study ◽  
Affinity Constant ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D3 levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D3 levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals.

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