Association of Vitamin D Receptor Polymorphisms with Amyloid-β Transporters Expression and Risk of Mild Cognitive Impairment in a Chilean Cohort

2020 ◽  
pp. 1-14
Author(s):  
Nohela B. Arévalo ◽  
Daniela P. Castillo-Godoy ◽  
Italo Espinoza-Fuenzalida ◽  
Nicole K. Rogers ◽  
Gonzalo Farias ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Vitamin D Receptor ◽  
Mononuclear Cells ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Mrna Levels ◽  
Vdr Gene ◽  
Vdr Polymorphisms

Background: Amyloid-β peptide (Aβ) deposition in Alzheimer’s disease (AD) is due to an imbalance in its production/clearance rate. Aβ is transported across the blood-brain barrier by LRP1 and P-gp as efflux transporters and RAGE as influx transporter. Vitamin D deficit and polymorphisms of the vitamin D receptor (VDR) gene are associated with high prevalence of mild cognitive impairment (MCI) and AD. Further, vitamin D promotes the expression of LRP1 and P-gp in AD-animal model brains. Objective: To associate VDR polymorphisms Apa I (rs7975232), Taq I (rs731236), and Fok I (rs2228570) with the risk of developing MCI in a Chilean population, and to evaluate the relationship of these polymorphisms to the expression of VDR and Aβ-transporters in peripheral blood mononuclear cells (PBMCs). Methods: VDR polymorphisms Apa I, Taq I, and Fok I were determined in 128 healthy controls (HC) and 66 MCI patients. mRNA levels of VDR and Aβ-transporters were evaluated in subgroups by qPCR. Results: Alleles A of Apa I and C of Taq I were associated with a lower risk of MCI. HC with the Apa I AA genotype had higher mRNA levels of P-gp and LRP1, while the expression of VDR and RAGE were higher in MCI patients and HC. For Fok I, the TC genotype was associated with lower expression levels of Aβ-transporters in both groups. Conclusion: We propose that the response to vitamin D treatment will depend on VDR polymorphisms, being more efficient in carriers of protective alleles of Apa I polymorphism.

scholarly journals Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Damir Raljević ◽  
Viktor Peršić ◽  
Elitza Markova-Car ◽  
Leon Cindrić ◽  
Rajko Miškulin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vitamin D ◽  
Coronary Artery ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
Vdr Gene Polymorphisms ◽  
Vdr Polymorphisms

Abstract Background Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms—Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)—in a cohort of CAD patients after acute myocardial infarction. Methods In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. Results The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. Conclusion The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

2021 ◽  
pp. 1-13
Author(s):  
Dong Bai ◽  
Junting Fan ◽  
Mengyue Li ◽  
Cuixia Dong ◽  
Yiming Gao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Digit Span ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Double Blind ◽  
Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged >  60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p <  0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p <  0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

scholarly journals VITAMIN D RECEPTOR GENE POLYMORPHISMS AND HAPLOTYPE ANALYSIS IN TYPE 2 DIABETES MELLITUS PATIENTS FROM NORTH INDIA

2017 ◽  
Vol 10 (10) ◽  
pp. 248
Author(s):  
Nancy Taneja ◽  
Rajesh Khadgawat ◽  
Shalini Mani
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Vitamin D Receptor ◽  
Mutant Allele ◽  
Haplotype Analysis ◽  
Vdr Gene ◽  
Vdr Polymorphisms

  Objective: Vitamin D receptor (VDR) mediated Vitamin D signaling is important for expression of insulin gene and glucose transporters, which help in glucose uptake by cells. Current evidence suggests that four common polymorphisms (FokI, BsmI, ApaI, TaqI) of VDR gene are associated with Type 2 diabetes mellitus (T2DM) in different populations. However, there is a scarcity of data on VDR polymorphisms from Indian population.Methods: In the current study, total genomic DNA was isolated from 100 well-characterized T2DM patients and 100 healthy controls. We investigated the prevalence of FokI and ApaI polymorphisms in VDR gene of these patients by polymerase chain reaction-restriction fragment length polymorphism-based method. Taking help of our previous published data on TaqI and BsmI polymorphisms in same patients, the haplotype study was also conducted. Statistical analysis of data was performed using SPSS 21.0 software. Haplotype and linkage disequilibrium analysis was performed by Haploview software.Results: Both the wild (TT) and mutant (CC) genotype of FokI polymorphism showed a significant difference between patients and controls (p<0.001 and p<0.001, respectively). The frequency of mutant allele (C) was also significantly higher in T2DM patients than the controls (p<0.001). In case of ApaI, frequency of wild (GG) and mutant (CC) genotype was significantly different in patients and controls (p=0.017 and p=0.034). As per haplotype analysis, the CACT haplotype was predicted to be of significance in patients and consists of mutant alleles of three polymorphisms (FokI, BsmI, ApaI). Conclusion: Our study supports the association of FokI and ApaI polymorphism in T2DM. The haplotype analysis also indicates that the combinations of mutant allele of different VDR polymorphisms are probably responsible for increased susceptibility of these individuals toward T2DM.

Amyloid imaging in dementia

2012 ◽  
Vol 23 (1) ◽  
pp. 43-60
Author(s):  
A Ashraf ◽  
P Mehta ◽  
P Edison
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Critical Evaluation ◽  
Amyloid Β ◽  
Amyloid Imaging ◽  
Therapeutic Window ◽  
Pharmacological Intervention ◽  
Early Event ◽  
Amyloid Β Peptide

SummaryA major advancement in the field of medicine has been the timely advent of amyloid imaging, which has allowed critical evaluation of the complex relationship between amyloid β peptide (Aβ) aggregation and Alzheimer's disease in vivo. Most importantly, amyloid imaging has the potential to detect Aβ in mildly affected as well as asymptomatic individuals, when the therapeutic window of opportunity might still be open to pharmacological intervention. It also shows significant promise in differential diagnosis of mild cognitive impairment or atypical dementias. Amyloid imaging studies support a model in which amyloid aggregation is considered an early event on the path of dementia, beginning insidiously in cognitively healthy individuals being accompanied by subtle cognitive, functional and structural brain alterations suggestive of incipient AD. As individuals progress to dementia, clinical decline and neurodegeneration accelerate and might proceed independently of amyloid accumulation. In this review we focus on amyloid imaging with particular emphasis on [11C]PIB in AD, mild cognitive impairment and other dementias, and discuss the advances made in this perplexing field.

scholarly journals The role of vitamin D receptor gene polymorphisms in gestational diabetes mellitus susceptibility: a meta-analysis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sai Liu
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Gestational Diabetes ◽  
Gene Polymorphism ◽  
Gestational Diabetes Mellitus ◽  
Vitamin D Receptor ◽  
Meta Analysis ◽  
Recessive Model ◽  
Vdr Gene ◽  
Vdr Polymorphisms

Abstract Background Gestational diabetes mellitus (GDM) is a common disease during pregnancy. The association of vitamin D receptor (VDR) polymorphisms with GDM is still controversial. This study aimed to assess the associations between VDR polymorphisms and GDM risk. Methods We searched Cochrane Library, PubMed, and Embase electronic database for all eligible studies published from Jan 1, 1980 to December 31, 2020 to conduct a Meta-analysis. We analyzed four VDR polymorphisms: BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570). Inclusion Criteria: (1) The data can be evaluated; (2) case–control study; and (3) meeting the Hardy–Weinberg’s law. Exclusion criteria: (1) Insufficient or extractable data; (2) Severe publication bias in the data; and (3) duplicate publications. We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls. Results We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls. The data showed that ApaI (rs7975232) VDR gene polymorphism was related with the risk of GDM for the comparison of CC vs AA and recessive model in overall population and FokI (rs2228570) VDR gene polymorphism was associated with the risk of GDM for recessive model in overall population. BsmI (rs1544410) polymorphism was not related with the risk of GDM in overall population. However, in the analysis of subgroups grouped by race, BsmI (rs1544410) has certain correlations. And, the data suggested the TaqI (rs731236) polymorphism was not associated with GDM. Conclusion Based on the meta-analysis, VDR ApaI (rs7975232) and FokI (rs2228570) polymorphisms increase susceptibility to GDM. In the future, it can be used to diagnose and screen molecular biomarkers for GDM patients.

scholarly journals Exclusive underexpression of vitamin D receptor exon 1f transcripts in tumors of primary hyperparathyroidism

2002 ◽  
pp. 671-675 ◽  
Author(s):  
P Correa ◽  
G Akerstrom ◽  
G Westin
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Direct Action ◽  
Parathyroid Glands ◽  
Mrna Levels ◽  
Vdr Gene ◽  
Dihydroxyvitamin D ◽  
Parathyroid Adenomas ◽  
Distal Promoter

OBJECTIVE: Primary hyperparathyroidism (pHPT) is characterized by excessive production of parathyroid hormone (PTH) due to parathyroid adenomas while uremic secondary HPT (sHPT) is caused by parathyroid hyperplasia in response to renal failure. Active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), with the vitamin D receptor (VDR) is involved in regulation of the calcium homeostasis together with PTH. In a feedback loop, 1,25-(OH)(2)D(3) has a direct action on the parathyroid gland to regulate PTH transcription, PTH secretion and cell proliferation. We have previously demonstrated reduced VDR mRNA expression in parathyroid adenomas and hyperplasia of sHPT using a probe detecting all 14 variant VDR transcripts expressed in parathyroid cells. Here we have assessed which of the 5'-terminal exon 1a, 1d and 1f variant VDR transcripts are reduced in pathological parathyroid glands. METHODS: The relative VDR/glyceraldehyde-3-phosphate dehydrogenase mRNA levels for each VDR exon were determined by real-time quantitative RT-PCR in five normal parathyroid glands, seventeen parathyroid adenomas and ten hyperplastic glands of sHPT. RESULTS: The results demonstrated exclusive underexpression of VDR exon 1f transcripts in parathyroid adenoma, while all measured VDR transcripts were reduced in secondary hyperplasia. CONCLUSIONS: We suggest that exclusive underexpression of VDR exon 1f transcripts in adenomas of pHPT, which derive from a distal promoter active in tIssues involved in calcium regulation by 1,25-(OH)(2)D(3), may either reflect a defective cell type-specific transcription factor or other physiologically important pathway(s) for tIssue-specific VDR gene expression.

scholarly journals Vitamin D Receptor (VDR) Gene Polymorphism in Patients Diagnosed with Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 200
Author(s):  
Maria Latacz ◽  
Dominika Rozmus ◽  
Ewa Fiedorowicz ◽  
Jadwiga Snarska ◽  
Beata Jarmołowska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Environmental Factors ◽  
Gene Polymorphism ◽  
Vitamin D Receptor ◽  
Nucleotide Polymorphisms ◽  
Vdr Gene ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Vdr Polymorphisms

Colorectal cancer (CRC) is one of the most commonly occurring neoplasias in humans. The prevalence of CRC rates is still rising. Although the exact background of the disease still remains unknown, it is believed that CRC may not only be a result of environmental factors, but also genetic ones. One of the mechanisms underlying CRC might be the vitamin D pathway, as CRC is the most closely linked neoplasia to vitamin D deficiency. This study shows a possible association of the vitamin D receptor (VDR) polymorphisms FokI, BsmI, ApaI, and TaqI with CRC susceptibility. A total of 103 patients diagnosed with CRC (61 men and 42 women, aged 57–82 years) and 109 healthy people (50 men and 59 women, aged 47–68 years) were genotyped using PCR-RFLP for FokI, BsmI, ApaI, and TaqI. None of the single nucleotide polymorphisms (SNPs) individually increased or decreased the risk of CRC. The evaluation of haplotypes revealed two that might enhance the likelihood of CRC development: taB (OR = 30.22; 95% CI 2.81–325.31; p = 0.01) and tAb (OR = 3.84; 95% CI 1.29–11.38; p = 0.01). In conclusion, genotyping is an easy and robust procedure that needs to be performed only once in a lifetime. A creation of a relevant SNP’s panel might contribute to the identification of the groups that are at the greatest risk of CRC.

scholarly journals Vitamin D and Vitamin D Receptor in Scleroderma Subtypes

2020 ◽  
pp. 19-24
Author(s):  
Kocak Ayse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Mrna Levels ◽  
Diffuse Type ◽  
Gene Expressions ◽  
Vdr Gene ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
Tgf Β1

Vitamin D Receptor (VDR) is a member of the nuclear hormone receptor family. 1,25(OH)2D, a form of metabolically active vitamin D3 form, is the ligand of VDR. When VDR and 1,25(OH)2D are connected, many genes start to molecular interaction reactions that will modulate the transcription. VDR has been shown to be a negative regulator of the transforming growth factor beta-1 / Smad (TGF-β1 / Smad) signalling pathway. TGF-β1 / Smad signalling is important in the pathogenesis of scleroderma (SSc). Vitamin D has pleiotropic effects including immunomodulatory and antifibrotic properties in scleroderma pathogenesis. The aim of this study was to investigate the expression of VDR and the levels of vitamin D in scleroderma subtypes and study the possible correlation between the two parameters. 28 SSc patients and 30 healthy controls were included in the study and they were classified according to the 2013 ACR / EULAR criteria and Rodnan Scores were calculated. 14 were of the limited type and 14 were of the diffuse type of scleroderma. Vitamin D levels were determined in serum. Vitamin D level was measured by chemiluminescence immunometric assay. VDR gene expression was determined by quantitative PCR in isolated RNAs from the blood. Changes in mRNA levels were analysed and beta-actin was used as the housekeeping gene. Also, TGF-β1 gene expressions were determined. VDR gene expressions in diffuse type scleroderma patients were significantly decreased compared to the control. TGF-β1 gene expressions were increased in diffuse type scleroderma. It was found that VDR gene expression in limited type scleroderma patients did not show any significant difference when compared to control. Vitamin D levels and VDR gene expressions showed no correlation in scleroderma subtypes. VDR gene expression decreased in patients with diffuse type scleroderma and showed negative correlation with the Rodnan score and TGF-β1 gene expressions. There was no significant difference between vitamin D and VDR levels.

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