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

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.

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

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00764-y ◽

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.

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Vitamin D receptor polymorphisms in overweight/obese chronic kidney disease patients undergoing hemodialysis

10.1101/2021.06.02.21258095 ◽

2021 ◽

Author(s):

Gokhan Bagci ◽

Can Huzmeli ◽

Ferhan Candan

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Vitamin D Receptor ◽

Laboratory Data ◽

Normal Weight ◽

Nucleotide Polymorphisms ◽

Vdr Gene ◽

Pcr Rflp

Background: Many studies were carried out to investigate the relationship between single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene with obesity. However, little is known about the role of VDR gene polymorphism with obesity in hemodialysis (HD) patients. Therefore, we aimed to investigate VDR gene TaqI, ApaI and FokI SNPs in overweight/obese HD patients. Methods: Seventy one normal weight and 68 overweight/obese HD patients were included in study. PCR-RFLP method was used for genotyping. Demographic and laboratory data obtained from medical records of patients. Results: For all three SNPs, no significant association was found between normal and overweight/obese patients (P>0.05). Lower HDL concentrations and higher levels of triglyceride (TG) and glucose were detected in the obese/overweight patients compared to normal weight (p<0.001 for HDL, and TG and p=0.023 for glucose). In obese/overweight patients, subjects with CC genotype of TaqI showed higher PTH level (717.1±616.4 pg/ml) than those TC genotype (342.7±360.8 pg/ml) and TT genotype (310.2±323.4 pg/ml) (p=0.028); higher TG level was found in patients with CC genotype of ApaI (627.3±653.0 mg/dl) compared to AA (223.3±156.6) and AC genotypes (193.1±85.4) (p<0.001). Obese/overweight patients carrying FokI TT genotype had higher glucose concentration compared to those carrying CC and CT genotypes (CC=183.4±128.4 mg/dl; TT=151.9±66.1 mg/dl; CT=107.6±41.9 mg/dl, p=0.008). Conclusions: Our study suggest that VDR TaqI, ApaI and FokI polymorphisms are not associated with obesity in HD patients. However, they might be increase the risk of secondary hyperparathyroidism, dyslipidemia, and hyperglycemia, which are among the most common obesity related comorbidities of chronic kidney disease.

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Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications

Scientific Reports ◽

10.1038/s41598-020-78125-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Katarzyna Kosik ◽

Dawid Szpecht ◽

Salwan R. Al-Saad ◽

Lukasz M. Karbowski ◽

Grażyna Kurzawińska ◽

...

Keyword(s):

Vitamin D ◽

Preterm Infants ◽

Vitamin D Receptor ◽

Gene Polymorphisms ◽

Active Form ◽

Vdr Gene ◽

Vdr Polymorphism ◽

Single Nucleotide ◽

Vdr Gene Polymorphisms ◽

Vdr Polymorphisms

AbstractThe vitamin D receptor (VDR), coded by the VDR gene, plays a pivotal role in executing cellular functions when bound by the active form of vitamin D. Gene polymorphisms in this receptor have been increasingly associated with a heightened state of vulnerability to certain diseases. However, limited data is available concerning the role of VDR gene polymorphisms in preterm infant complications. In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The results show that BPD was almost four times more likely in infants with the genotype CC of ApaI (rs7975232) (OR 3.845; p = 0.038). While both BPD and NEC were 2.1 times more likely to occur in preterm infants with the allele C of ApaI (rs7975232) (respectively: OR 2.111 and OR 2.129, p < 0.05). The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant.

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Tu1375 Strong Association of Single Nucleotide Polymorphisms of Vitamin D Receptor Gene, BsmI, and Colorectal Cancer in Asian Population

Gastroenterology ◽

10.1016/s0016-5085(16)33000-1 ◽

2016 ◽

Vol 150 (4) ◽

pp. S888

Author(s):

Prapimphan Aumpansub ◽

Kessarin Thanapirom ◽

Surbpong Tanasanvimon ◽

Satimai Aniwan ◽

Sirinporn Suksawatamnuay ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Single Nucleotide Polymorphisms ◽

Vitamin D Receptor ◽

Receptor Gene ◽

Strong Association ◽

Asian Population ◽

Vitamin D Receptor Gene ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Vitamin D receptor, vitamin D binding protein and CYP27B1 single nucleotide polymorphisms and susceptibility to viral infections in infants

Scientific Reports ◽

10.1038/s41598-021-93243-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria Zacharioudaki ◽

Ippokratis Messaritakis ◽

Emmanouil Galanakis

Keyword(s):

Vitamin D ◽

Single Nucleotide Polymorphisms ◽

Viral Infection ◽

Vitamin D Receptor ◽

Viral Infections ◽

Binding Protein ◽

Genotypic Differences ◽

Nucleotide Polymorphisms ◽

Vitamin D Binding Protein ◽

Single Nucleotide

AbstractThe role of vitamin D in innate and adaptive immunity is recently under investigation. In this study we explored the potential association of genetic variances in vitamin D pathway and infections in infancy. Τhis prospective case–control study included infants 0–24 months with infection and age-matched controls. The single nucleotide polymorphisms of vitamin D receptor (VDR) gene (BsmI, FokI, ApaI, TaqI), vitamin D binding protein (VDBP) (Gc gene, rs7041, rs4588) and CYP27B1 (rs10877012) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In total 132 infants were enrolled, of whom 40 with bacterial and 52 with viral infection, and 40 healthy controls. As compared to controls, ΤaqI was more frequent in infants with viral infection compared to controls (p = 0.03, OR 1.96, 95% CI 1.1–3.58). Moreover, Gc1F was more frequent in the control group compared to infants with viral infection (p = 0.007, OR 2.7, 95% CI 1.3–5.6). No significant differences were found regarding the genetic profile for VDR and VDBP in infants with bacterial infection compared to the controls and also regarding CYP27B1 (rs10877012) between the studied groups. Genotypic differences suggest that vitamin D pathway might be associated with the host immune response against viral infections in infancy.

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

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01959-x ◽

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.

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i10.20453 ◽

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.

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Association of low penetrance vitamin D receptor Tru9I (rs757343) gene polymorphism with risk of premenopausal breast cancer

Journal of International Medical Research ◽

10.1177/0300060518761304 ◽

2018 ◽

Vol 46 (5) ◽

pp. 1801-1814 ◽

Cited By ~ 1

Author(s):

Mehir un Nisa Iqbal ◽

Syed Amir Maqbool ◽

Taseer Ahmed Khan

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Vitamin D Receptor ◽

Nucleotide Polymorphism ◽

Vdr Gene ◽

Premenopausal Breast Cancer ◽

Single Nucleotide ◽

Polymerase Chain ◽

Age Range ◽

Control Study

Objective The aim of this study was to determine whether a novel polymorphism ( Tru9I) in the low penetrance vitamin D receptor (VDR) gene is associated with risk of premenopausal breast cancer (BC). Methods This case-control study included 228 patients with BC and 503 healthy women living in Pakistan who were analyzed for the VDR Tru9I (rs757343) single nucleotide polymorphism. BC cases were histopathologically confirmed, and all healthy controls were age-matched with patients (age range, 20–45 years). DNA was extracted, and the polymerase chain reaction and restriction fragment length polymorphism assays were performed. Results The VDR Tru9I polymorphism was not significantly associated with premenopausal BC. However, the risk of BC was associated with the ‘uu’ genotype (odds ratio [OR], 1.141; 95% confidence interval [95% CI], 0.206–6.317). Further, mutant Tru9I was significantly associated with Grade IV carcinoma (OR, 5.36; 95% CI, 1.181–24.338). Conclusion The VDR Tru9I ‘uu’ genotype may increase the risk of premenopausal BC.

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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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