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VDR Polymorphisms (vdr + polymorphism)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men

DIABETIC MEDICINE, Issue 6 2003
J. R. Ortlepp
Abstract Aims Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor (VDR), which has been found to be associated with bone mineral density, has been reported to be also associated with Type 2 diabetes mellitus (DM). To test the influence of the VDR polymorphism on fasting glucose in healthy young men before the onset of Type 2 DM, we studied a homogeneous population of aircrew members. Methods A total of 1539 individuals were recruited during routine medical qualification for flying duty. Physical activity was assessed in all individuals and categorized into low physical activity (, 3 h per week) and high physical activity (> 3 h per week). The BsmI VDR polymorphism was analysed by polymerase chain reaction. On the day of blood testing the individuals were fasting for at least 8 h overnight. Serum glucose was measured within 60 min after sampling venous blood. Results In young males with low physical activity (n = 752) gene carriers with the VDR genotype BB (n = 137) have significantly (P < 0.001) higher levels of fasting glucose (5.61 ± 0.49 mmol/l) than gene carriers with the genotype Bb (n = 370; 5.44 ± 0.44 mmol/l) or bb (n = 245; 5.38 ± 0.44 mmol/l). Of BB gene carriers, 47% had fasting glucose levels > 5.55 mmol/l compared with 36% of Bb gene carriers and 34% of bb gene carriers (P = 0.018). This effect is absent in gene carriers with high physical activity (n = 787). Conclusions The VDR genotype is associated with altered fasting glucose levels in young men with low physical activity. If this association is confirmed in other populations it might be worthwhile studying the particular benefits of an exercise programme in dependents of the VDR genotype. Diabet. Med. 20, 451,454 (2003) [source]

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2001
J. R. Garcia-Lozano
The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D. [source]

Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population

INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007
Wataru Obara
Aim: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)2D3 and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. Methods: To analyze risk of RCC depending on VDR polymorphism, a case,control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. Results: Significant differences in the ApaI genotype were observed between RCC patients and controls (,2 = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21,5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). Conclusion: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted. [source]

Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis

HEPATOLOGY, Issue 1 2002
Arndt Vogel
Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune-mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25-Dihydroxyvitamin D3 has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. In this study VDR polymorphisms were analyzed in 123 patients with AIH, 74 patients with PBC, and 214 controls. VDR polymorphisms were assessed by BsmI, TaqI, ApaI, and Fok endonuclease digestion after specific polymerase chain reaction (PCR) amplification. We found a significant association between the BsmI polymorphisms in PBC patients in comparison with controls (,2 = 9.49, P = .009). Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls (,2 = 9.71, P = .008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases. [source]

Haplotype and genotypes of the VDR gene and cutaneous melanoma risk in non-Hispanic whites in Texas: A case,control study

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2008
Chunying Li
Abstract In a hospital-based case,control study of 805 non-Hispanic whites with cutaneous melanoma and 841 cancer-free age-, sex- and ethnicity-matched control subjects, 3 VDR polymorphisms (i.e., TaqI, BsmI and FokI) were genotyped using blood samples collected between 1994 and 2006. We tested the hypothesis that the haplotypes and combined genotypes of these polymorphisms were associated with melanoma risk by interacting with known risk factors. Haplotypes t-B-F (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.34,0.80) and t-B-f (adjusted OR, 0.51; CI, 0.27,0.94) were associated with a reduced risk when compared to T-b-f. The combined genotypes Tt+tt/Bb+BB/Ff+ff (adjusted OR, 0.69; CI, 0.52, 0.90) and Tt+tt/Bb+BB/FF (adjusted OR, 0.58; CI, 0.43, 0.78) were also associated with reduced risk, whereas the combined genotype TT/Bb+BB/Ff+ff genotype (adjusted OR, 2.35; CI, 1.13, 4.98) was associated with increased risk when compared to TT/bb/Ff+ff genotypes. On multivariate analysis, only the TaqI polymorphism was an independent risk factor, while the FokI polymorphism interacted with skin color (p = 0.029), moles (p = 0.017) and first-degree relatives with any cancer (p = 0.013) in modifying risk. Together, these findings suggest that VDR polymorphisms may directly affect or modify the risk associated with known melanoma risk factors. Larger, population-based studies are needed to replicate our findings. © 2008 Wiley-Liss, Inc. [source]

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis

Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008
C. L. NOBLE
Summary Background, Osteoporosis is a recognized complication of inflammatory bowel disease (IBD). Aim, To investigate the role of environmental factors and vitamin D receptor (VDR) variants on the prevalence of osteoporosis. Methods, DEXA scans and case note review were performed on 440 IBD patients from 1997 to 2006. All the IBD patients and 240 healthy controls were genotyped for VDR variants Taq -1 and Apa -1 using PCR-RFLP. Results, Osteoporosis and osteopenia rates were 15% and 18% for IBD, 16% and 18% for Crohn's disease (CD) and 13% and 19% for ulcerative colitis, respectively. On univariate analysis of the CD patients, low body mass index (BMI, <18.5) and smoking status (P = 0.008 and 0.005 respectively) were associated with osteoporosis and osteopenia. Low BMI was also associated with osteoporosis on multivariate analysis in CD (P = 0.021, OR 5.83, CI 1.31,25.94). No difference was observed between Taq -1 and Apa -1 VDR polymorphisms in IBD, CD, ulcerative colitis and healthy controls. However, CD males were more likely to carry the variant Taq -1 polymorphism than healthy controls males (P = 0.0018, OR 1.94, CI 1.28,2.92) and female CD patients (P = 0.0061, OR 1.60, CI 1.17,2.44). Conclusions, In this well-phenotyped cohort of IBD patients, a relatively low prevalence of osteoporosis was observed. Low BMI was the only independent risk factor identified to be associated with osteoporosis. [source]

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk

THE PROSTATE, Issue 9 2007
Bahar Mikhak
Abstract BACKGROUND The vitamin D receptor (VDR) is required for actions of vitamin D. The binding of 1,25-dihydroxyvitamin D to the VDR on prostatic epithelial cells prompts the regulation of cancer-related genes. METHODS We conducted a nested case-control study in the Health Professionals Follow-up Study to investigate the role of the VDR Cdx2, Fok1, and Bsm1 gene polymorphisms and associated haplotypes and their interaction with plasma vitamin D metabolites in relation to prostate cancer (PC) risk. RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum ,7; P,=,0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (,15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum ,7) (P for interaction,=,0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (,26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction,=,0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Prostate 67: 911,923, 2007. © 2007 Wiley-Liss, Inc. [source]

Vitamin D and systemic cancer: is this relevant to malignant melanoma?

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2002
J.E. Osborne
Summary 1,25-dihydroxyvitamin D3[1,25(OH)2D3] is a well-known potent regulator of cell growth and differentiation and there is recent evidence of an effect on cell death, tumour invasion and angiogenesis, which makes it a candidate agent for cancer regulation. The classical synthetic pathway of 1,25(OH)2D3 involves 25- and 1,-hydroxylation of vitamin D3, in the liver and kidney, respectively, of absorbed or skin-synthesized vitamin D3. There is recent focus on the importance in growth control of local metabolism of 1,25(OH)2D3, which is a function of local tissue synthetic hydroxylases and particularly the principal catabolizing enzyme, 24-hydroxylase. The classical signalling pathway of 1,25(OH)2D3 employs the vitamin D nuclear receptor (VDR), which is a transcription factor for 1,25(OH)2D3 target genes. Effects of this pathway include inhibition of cellular growth and invasion. Cytoplasmic signalling pathways are increasingly being recognized, which similarly may regulate growth and differentiation but also apoptosis. 1,25(OH)2D3 has a major inhibitory effect on the G1/S checkpoint of the cell cycle by upregulating the cyclin dependent kinase inhibitors p27 and p21, and by inhibiting cyclin D1. Indirect mechanisms include upregulation of transforming growth factor-, and downregulation of the epidermal growth factor receptor. 1,25(OH)2D3 may induce apoptosis either indirectly through effects on the insulin-like growth receptor and tumour necrosis factor-, or more directly via the Bcl-2 family system, the ceramide pathway, the death receptors (e.g. Fas) and the stress-activated protein kinase pathways (Jun N terminal kinase and p38). Inhibition of tumour invasion and metastasis potential has been demonstrated and mechanisms include inhibition of serine proteinases, metalloproteinases and angiogenesis. The lines of evidence for an effect of vitamin D3 in systemic cancer are the laboratory demonstration of relevant effects on cellular growth, differentiation, apoptosis, malignant cell invasion and metastasis; epidemiological findings of an association of the occurrence and outcome of cancers with derangements of vitamin D3/1,25(OH)2D3 and the association of functional polymorphisms of the VDR with the occurrence of certain cancers. In addition, vitamin D3 analogues are being developed as cancer chemotherapy agents. There is accumulating evidence that the vitamin D3/1,25(OH)2D3/VDR axis is similarly important in malignant melanoma (MM). MM cells express the VDR, and the antiproliferative and prodifferentiation effects of 1,25(OH)2D3 have been shown in cultured melanocytes, MM cells and MM xenografts. Recently, an inhibitory effect on the spread of MM cells has been demonstrated, low serum levels of 1,25(OH)2D3 have been reported in MM patients and the VDR polymorphisms have been shown to be associated with both the occurrence and outcome of MM. The relationship between solar irradiation and MM is more complex than for the systemic cancers. As in other cancers, there is evidence of a protective effect of vitamin D3 in MM, but ultraviolet radiation, which is a principal source of vitamin D3, is mutagenic. Further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. Meanwhile, it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM. [source]