P028 The Apa I polymorphism in the Vitamin D receptor gene is associated with a stricturing behaviour in Crohn′s disease patients

Abstract Background Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors that plays an immunomodulatory role in the gastrointestinal tract through binding Vitamin D. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been related to inflammatory bowel disease. Indeed, Crohn′s disease (CD) patients carrying the Taq I polymorphism in VDR gene run a higher risk of developing a penetrating behaviour. We analyse here the association between the VDR SNPs Taq I, Bsm I, Apa I and Fok I and the clinical characteristics of CD. Methods DNA was extracted from blood samples from 80 patients diagnosed with CD from the Hospital of Manises (Valencia). Four polymorphisms identified in the VDR gene (Bsm I, Fok I, Apa I and Taq I) were genotyped using PCR-RFLP. Clinical data for each patient, including the Montreal classification was collected. Statistical significance was done using contingency tables and measured by Chi-squared or Fisher test. Results Results reveal a strong linkage disequilibrium between Apa I, Bsm I and Taq I polymorphisms. Apa I appears next to Bsm I and it is negatively associated with Taq I. The presence of at least a risk allele for Apa I is significantly associated with a stricturing behaviour in CD patients (P=0.014, Table 1), while the ancestral genotype (WT) of Apa I was significantly associated with a penetrating behaviour (P=0.062, Table 2). Finally, the presence of the risk genotype of Apa I is associated with a non-colonic location of the disease (P=0.059, Table 3). Fok I was not significantly associated with any of the parameters analysed. Conclusion Our results in CD patients reveal that the presence of the risk allele of Apa I in the VDR genotype is associated with a stricturing behaviour and tends towards a non-colonic location of the disease. This suggests that the analysis of this polymorphism may be useful for clinicians as a prognostic factor.

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Association of the polymorphism of the vitamin D receptor gene (VDR) with the risk of leprosy in the Brazilian Amazon

Bioscience Reports ◽

10.1042/bsr20204102 ◽

2021 ◽

Author(s):

Jasna Letícia Pinto Paz ◽

Maria do Perpétuo Socorro Corrêa Amador Silvestre ◽

Letícia Siqueira Moura ◽

Ismari Perini Furlaneto ◽

Yan Corrêa Rodrigues ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Genetic Factors ◽

Receptor Gene ◽

Mycobacterium Leprae ◽

Nucleotide Polymorphisms ◽

Vdr Gene ◽

Single Nucleotide ◽

The Relationship

The transmission and evolution of leprosy depends on several aspects, including immunological and genetic factors of the host, as well as genetic factors of Mycobacterium leprae. This study evaluated the association of single nucleotide polymorphisms (SNPs) on the FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) regions of the vitamin D receptor (VDR) gene with leprosy. A total of 405 individuals were evaluated, composed by groups of 100 multibacillary and 57 paucibacillary patients, and 248 healthy contacts. Blood samples were collected from patients and contacts. The genotyping was performed by sequencing of the interest regions. The alleles of the studied SNPs, and of SNP FokI genotypes, were not associated with leprosy. For the SNP on TaqI region, the relationship between the tt genotype, and for the SNP ApaI, the AA genotype, revealed an association with susceptibility to MB form, while Aa genotype with protection. The extended genotypes AaTT and AaTt of ApaI and TaqI were associated with protection to against MB form. Futher studies analyzing the expression of the VDR gene and the correlation with its SNPs might help to clarify the role of polymorphisms on the immune response in leprosy.

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Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

Acta Endocrinologica ◽

10.1530/eje.0.1450181 ◽

2001 ◽

pp. 181-186 ◽

Cited By ~ 89

Author(s):

WZ Ye ◽

AF Reis ◽

D Dubois-Laforgue ◽

C Bellanne-Chantelot ◽

J Timsit ◽

...

Keyword(s):

Vitamin D ◽

Insulin Secretion ◽

Vitamin D Receptor ◽

Age Of Onset ◽

Major Gene ◽

Receptor Gene ◽

Nucleotide Polymorphisms ◽

Vdr Gene ◽

Receptor Gene Polymorphisms

OBJECTIVE: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). METHOD: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls. RESULTS: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was < or =45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) (31.7+/-6.7 kg/m2, P=0.0058) and an increased prevalence of obesity (81%, P=0.005) with respect to heterozygous subjects (27.9+/-5.0 kg/m2; 46%) or homozygous subjects for the t-allele (27.7+/-5.0 kg/m2; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% confidence interval (CI), 1.64-14.76; P=0.0056). CONCLUSION: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.

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Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

Egyptian Liver Journal ◽

10.1186/s43066-020-00067-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ghada M. Galal ◽

Ahmad Abudeif ◽

Nagwa Sayed Ahmed ◽

Nahed Fathallah Fahmy ◽

Abeer Sheneef ◽

...

Keyword(s):

Vitamin D ◽

Liver Cirrhosis ◽

Vitamin D Receptor ◽

Receptor Gene ◽

Experimental Studies ◽

Nucleotide Polymorphisms ◽

Vdr Gene ◽

Abdominal Ultrasonography ◽

Increased Risk ◽

Significant Difference

Abstract Background HCV is a major risk factor for HCC; however, the exact mechanism of hepatocarcinogenesis is still not fully understood. Host genetic factors have been reported to play a significant role. Experimental studies support the tumor inhibitory effect of vitamin D on HCC cells. Several single nucleotide polymorphisms (SNPs) have been depicted in the vitamin D receptor (VDR) gene. We aimed to assess whether any of these polymorphisms could be significantly associated with increased risk of HCC. Results This study was conducted on 76 patients with HCV-related liver cirrhosis (48 patients had HCC on top of cirrhosis, and the other 28 had liver cirrhosis only). All patients underwent full medical history assessment, clinical examination, laboratory investigations, abdominal ultrasonography, and genotyping of the VDR gene. HCC patients had a significantly higher frequency of ApaI CC genotype compared with those patients without HCC. There is no statistically significant difference between the studied groups at any TaqI genotypes, but the carriage of the ApaI CC genotype had a significant association with liver disease severity in both patients groups compared with ApaI CA/AA genotypes. The carriage of the ApaI CC genotype was an independent predictor for HCC in HCV-related liver cirrhosis. Conclusions VDR ApaI polymorphism is significantly associated with the development of HCC; thus, ApaI CC genotype could be used as an important molecular marker to predict the risk of HCC in patients with HCV-related liver cirrhosis.

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Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200805101302 ◽

2020 ◽

Vol 20 ◽

Author(s):

Hamidreza Totonchi ◽

Ramazan Rezaei ◽

Shokoofe Noori ◽

Negar Azarpira ◽

Pooneh Mokarram ◽

...

Keyword(s):

Metabolic Syndrome ◽

Vitamin D ◽

Vitamin D Receptor ◽

Protective Factor ◽

Meta Analysis ◽

Receptor Gene ◽

Fixed Effect Model ◽

Fixed Effect ◽

Vdr Gene ◽

Effect Model

Introduction: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. Methods: All accessible studies reporting the association between the FokI (rs2228570) or / and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. Results: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. Conclusion: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in prevention or treatment of the MetS.

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FokI polymorphism of the vitamin D receptor (VDR) gene and susceptibility to tuberculosis: evidence through a meta-analysis

10.21203/rs.3.rs-266491/v1 ◽

2021 ◽

Author(s):

Upendra Yadav ◽

Pradeep Kumar ◽

Vandana Rai

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Meta Analysis ◽

Receptor Gene ◽

Asian Population ◽

Recessive Model ◽

Dominant Model ◽

Vdr Gene ◽

Exact Relation ◽

Significance Level

Abstract Background: Tuberculosis is one of the top ten causes of deaths worldwide. The deficiency of vitamin D was reported to be associated with the increased susceptibility of tuberculosis. Various previous reports were published to check the association of FokI polymorphism of the vitamin D receptor gene with tuberculosis risk. But their results were inconsistent so, we performed a meta-analysis to know the exact relation of the two.Methods: Different databases were screened up to November, 2020 with the keywords “Vitamin D receptor”, “VDR”, and “FokI”, along with “Tuberculosis” and “TB” to find the suitable articles. All the statistical analyses were performed by the Open Meta-Analyst program and all p-values were two-tailed with a significance level of 0.05.Results: No statistically significant association was observed in the allele contrast model (ORfvs.F= 1.11, 95%CI= 0.99-1.24, p= 0.05, I2= 73.46%), in the dominant model (ORff+Ffvs.FF= 1.11, 95%CI= 0.96-1.28, p= 0.14, I2= 71.39%), and in the co-dominant model (ORFfvs.FF= 1.05, 95%CI= 0.92-1.21, p= 0.41, I2= 65.97%). However, a significant association was found in the homozygote model (ORffvs.FF= 1.32, 95%CI= 1.03-1.69, p= 0.02, I2= 67.02%) and in the recessive model (ORFF+Ff vs.ff= 1.26, 95%CI= 1.03-1.54, p= 0.02, I2= 58.01%). Further analysis was performed on the bases of the ethnicity. In Asian population a significant association was found in the homozygote model (ORffvs.FF= 1.57, 95%CI= 1.12-2.21, p= 0.008, I2= 70.37%) and in the recessive model (ORFF+Ff vs.ff= 1.43, 95%CI= 1.08-1.89, p= 0.01, I2= 63.13%).Conclusion: In conclusion, a significant association of FokI with tuberculosis susceptibility was found in the overall analysis and in the Asian population.

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THE ASSOCIATION OF AРAI-POLYMORPHISM OF VITAMIN D RECEPTOR GENE (VDR) WITH DEVELOPMENT OF GENERALIZED PARODONTITIS IN UKRAINIAN POPULATION

Wiadomości Lekarskie ◽

10.36740/wlek201907105 ◽

2019 ◽

Vol 72 (7) ◽

pp. 1253-1257

Author(s):

Ilia G. Fomenko ◽

Viktoriia Yu. Harbuzova ◽

Olha A. Obukhova ◽

Vladislav V. Pohmura ◽

Inna A. Plakhtiienko ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Receptor Gene ◽

Smoking Habit ◽

Binary Logistic Regression ◽

Control Group ◽

Vitamin D Receptor Gene ◽

Vdr Gene ◽

Comparison Groups ◽

Relationship Of

Introduction: At present, it is believed that the genetic component is important in the pathogenesis of periodontitis. One of the candidate genes that are of major importance in the development of the disease is the vitamin D receptor gene (VDR). The association of its genetic polymorphisms, in particular Apal, with periodontitis in different populations of the world is proved. The aim: To study the association of the Apal-polymorphism VDR gene with the development of generalized periodontitis in the Ukrainian population. Materials and methods: Patient genotypes were determined by polymerase chain reaction with subsequent analysis of restriction fragment length (PCR-RFLP) from buccal epithelium 116 patients with generalized periodontitis (GP) and 67 individuals of control group. Statistical analysis was performed by using SPSS-17,0 program. Results: As a result of the performed studies, it was shown that in the group of patients with GP, the ratio of homozygous for the main allele (a/a), heterozygote (a/A) and homozygote for the minor allele (A/A) was 26 (22,4%), 62 (53,4%), 28 (24,2%), and in control group – 25 (37,3%), 27 (40,3%), 15 (22,4%), respectively. The distribution of genotypes in the comparison groups was not statistically significant (P = 0,084). By the method of binary logistic regression in the framework of the additive inheritance model (a/A vs a/a), a reliable relationship of the genotype with the Apal-polymorphism of the VDR gene was established with the development of generalized periodontitis (Р=0,029). It was shown that in heterozygotes (a/A) the risk of GP in 2,208 (95% CI = 1,084-4,496) times is higher than in homozygotes of the main allele (a/a). After adjusting for age, sex, smoking habit, BMI, the reliability of these results was maintained (P = 0,030). Conclusions: The ApaI-polymorphism of the VDR gene is associated with the development of generalized periodontitis in the Ukrainian population.

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The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk

Cancers ◽

10.3390/cancers12061379 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1379

Author(s):

Ippokratis Messaritakis ◽

Asimina Koulouridi ◽

Maria Sfakianaki ◽

Konstantinos Vogiatzoglou ◽

Nikolaos Gouvas ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Vitamin D Receptor ◽

Bacillus Stearothermophilus ◽

Receptor Gene ◽

Stage Iv ◽

Colorectal Carcinogenesis ◽

Thermus Aquaticus ◽

Vdr Gene

Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236; Thermus aquaticus I (TaqI), rs7975232; Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570; Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p < 0.001), leading to significantly decreased survival (p < 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p < 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

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Allelic variations in coding regions of the vitamin D receptor gene in dairy cows and potential susceptibility to periparturient hypocalcaemia

Journal of Dairy Research ◽

10.1017/s0022029912000465 ◽

2012 ◽

Vol 79 (4) ◽

pp. 423-428 ◽

Cited By ~ 4

Author(s):

Carolin Deiner ◽

Maria Reiche ◽

Dirk Lassner ◽

Desirée Grienitz ◽

Sven Twardziok ◽

...

Keyword(s):

Vitamin D ◽

Dairy Cows ◽

Vitamin D Receptor ◽

Bos Taurus ◽

Post Partum ◽

Receptor Gene ◽

Vdr Gene ◽

Coding Regions ◽

Vdr Gene Polymorphisms ◽

Clinical Records

Periparturient hypocalcaemia (milk fever) is a disorder of Ca metabolism in dairy cattle primarily affecting multiparous cows. The major reasons for the rapid decrease of blood Ca concentration after calving are the prompt increase of Ca secretion into the colostrum and the delayed activation of Ca regulation mechanisms including calcitriol, a metabolite of vitamin D. In man, vitamin D receptor (VDR) gene polymorphisms are reported to be associated with disturbances of Ca metabolism, whereas data confirming the same in dairy cows are still missing. Moreover, polymorphisms that only affect non-coding regions are sometimes difficult to ascribe to a specific disorder as pathways and unequivocal links remain elusive. Therefore, the idea of the present study was to investigate in a small group of dairy cows with documented clinical records whether polymorphisms in the coding regions of the VDR gene existed and whether these potentially found variations were correlated with the incidence of periparturient hypocalcaemia. For this purpose, blood DNA was isolated from 26 dairy cows in their 4th to 6th lactation, out of which 17 had experienced hypocalcaemia at least once, whereas 9 cows had never undergone periparturient hypocalcaemia in their lifetime. The 10 VDR exons and small parts of adjacent introns were sequenced and compared with the Bos taurus VDR sequence published on NCBI based on the DNA of one Hereford cow. In total, 8 sequence alterations were detected in the fragments, which were primarily heterozygous. However, only 4 of them were really located on exons thereby potentially causing changes of the encoded amino acid of the VDR protein, but were not correlated with the incidence of periparturient hypocalcaemia. Certainly, this lack of statistical correlation could be due to the small number of animals included; anyhow, it was not encouraging enough to initiate a larger study with hundreds of cows and document blood Ca levels post partum for at least four lactations.

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Interaction between a variant of vitamin D receptor gene and a posteriori dietary patterns on metabolic syndrome and its components

Nutrition & Food Science ◽

10.1108/nfs-11-2017-0254 ◽

2018 ◽

Vol 48 (5) ◽

pp. 780-794 ◽

Cited By ~ 2

Author(s):

Fatemeh Shokrzadeh ◽

Zahra Aslani ◽

Abbas Rahimi-Foroushani ◽

Sakineh Shab-Bidar

Keyword(s):

Metabolic Syndrome ◽

Vitamin D ◽

Vitamin D Receptor ◽

Dietary Patterns ◽

Receptor Gene ◽

Cross Sectional Study ◽

Serum Glucose ◽

Vdr Gene ◽

Cross Sectional ◽

Content Type

Purpose This paper aims to investigate whether the interaction between vitamin D receptor (VDR) FokI polymorphism and dietary patterns is associated with metabolic syndrome (MetS) and its components. Design/methodology/approach In total, 304 Iranians were enrolled in this cross-sectional study. Dietary patterns were identified using factor analysis. Fasting serum glucose and lipid profile were also assessed. FokI polymorphism of the VDR gene was genotyped using the restriction fragment length polymorphism method. Findings Individuals in third tertile of “Unhealthy Patterns had greater odds for MetS (odds ratio: 2.9; 95 per cent CI: 1.3, 6.1; P for trend = 0.03) compared to those in first tertile. Significant results disappeared after controlling for covariates (p = 0.09). There was no significant relationship between adherence to ‘Healthy Pattern’ and odds of MetS (p = 0.55). There were not any interactions between FokI polymorphism and major dietary patterns associated with MetS. Originality/value No evidence found for the interaction between polymorphism FokI and major dietary patterns associated with MetS and its components in Iranian subjects. Genome-wide association techniques are needed to assess the direct effect of this polymorphism on MetS.

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