What is the VDR Gene?

A look at some of the research:

significant findings:

Vitamin D Receptor Gene Polymorphism in Patients with Sarcoidosis
http://ajrccm.atsjournals.org/cgi/reprint/160/4/1107

The active form of vitamin D, 1,25-dihydroxyvitamin D3, is known to be produced at sites of granulomatous reactions in sarcoidosis. 1,25-dihydroxyvitamin D3 has multiple immunomodulatory effects, and acts as a promoter of multinucleated giant cell formation. Polymorphism of the vitamin D receptor (VDR) gene has recently been shown to be related to bone mineral density, and also associated with hyperparathyroidism and risk of prostatic carcinoma. Considering that this might affect sarcoidosis, we investigated polymorphism of the VDR gene in 101 patients with sarcoidosis and 105 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism. In the patients with sarcoidosis, the BB, Bb, and bb genotypes accounted for 1.0%, 37.6%, and 61.4%, whereas in healthy control subjects the figures were 1.0%, 20.0%, and 79.0%, respectively. The difference in the genotype distribution between healthy control subjects and sarcoidosis patients was significant (p < 0.05) with the frequency of the B allele being elevated (p < 0.05). From the result, we suggest that in VDR gene polymorphism the B allele might be a genetic risk factor for sarcoidosis.

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature.
http://www.ncbi.nlm.nih.gov/pubmed/19667145

CONCLUSION: Significant associations with VDR polymorphisms have been reported in cancer of the breast (Fok1, Bsm1, Taq1, Apa1, poly (A)), prostate (Fok1, Bsm1, Taq1, poly (A)), skin (Fok1, Bsm1, A-1210), colorectum (Fok1, Bsm1), ovary (Fok1, Apa1) and bladder (Fok1), and in renal cell carcinoma (Taq1, Apa1). However, conflicting data have been reported for most malignancies. After careful evaluation of the actual literature, it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (MM) (Fok1). Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer (Fok1), breast cancer (Bsm1, Taq1), MM (Bsm1) and renal cell carcinoma (Taq1).

Vitamin D Receptor Gene Polymorphism Is Associated with Graves’ Disease in the Japanese Population1
http://jcem.endojournals.org/cgi/content/abstract/85/12/4639

Susceptibility to Graves’ disease (GD), which is determined by environmental and genetic factors, is conferred by genes in the human leukocyte antigen (HLA) and genes unlinked to HLA, including the CTLA-4 gene. We recently described the association of GD with the vitamin D receptor (VDR) exon 2 initiation codon (VDR-FokI) polymorphism. An association of some VDR genotypes with osteoporosis, primary hyperparathyroidism, and some autoimmune diseases, such as insulin-dependent diabetes mellitus and multiple sclerosis, has been reported. We investigated the distribution of VDR gene polymorphism in 180 Japanese patients with GD (48 males and 132 females) and 195 controls (67 males and 128 females). A VDR allelic polymorphism was assessed by BsmI endonuclease restriction after specific PCR amplification. Genotypic polymorphism was clearly defined as BB (no restriction site on both alleles), bb (restriction site on both alleles), or Bb (heterozygous). The distribution of genotype frequencies differed between patients with GD and controls ({chi}2 = 7.53; 2 degrees of freedom; P = 0.023). The relative risk conferred by at least 1 B allele (BB or Bb) was 1.5. We also found an association between VDR-ApaI polymorphism and GD. No relation was detected between this polymorphism and the VDR-FokI polymorphism in the patients. The present results support the association of the VDR gene with GD in Japanese by showing that the VDR gene could be a non-HLA-linked gene predisposing an individual to GD. The role of the VDR gene polymorphism should be further studied in other populations, and the distribution of other polymorphisms, such as the polyadenylase polymorphism further down the VDR 3'-untranslated region, should be studied in terms of GD susceptibility.

Vitamin D Receptor (VDR) Gene Polymorphism is Associated with Left Ventricular (LV) Mass and Predicts LVH Progression in End Stage Renal Disease (ESRD) Patients
http://www.jbmr.org/details/journalArticle/518125/Vitamin_D_Receptor_VDR_Gene_Polymorphism_is_Associated_with_Left_Ventricular_LV_.html
Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in ESRD patients. Vitamin D deficiency and/or disturbed vitamin D signalling has been implicated in LVH in experimental models. Because the BsmI VDR gene polymorphism may alter the VDR function, we performed a cross-sectional and longitudinal study in a cohort of 182 dialysis patients to investigate 1) the relationship between BsmI VDR gene polymorphism and LV mass index (LVMI) measured by echocardiography, and 2) the predictive power of this polymorphism for progression in LVH over a 18±2 months follow up. As reference group we used 175 healthy subjects matched to the study population as for age and sex.
The distribution of BsmI genotypes did not significantly deviate from Hardy-Weinberg equilibrium either in patients or in the control group of healthy subjects. The frequency of the B allele of BsmI polymorphism (40.4 % ) in dialysis patients was similar to that of healthy control subjects (38.6% ) and the number of B-alleles was directly related to LVMI (r=0.20, p=0.007). This relationship remained robust (=0.19, p=0.006) in multivariate analysis adjusting for traditional and non-traditional risk factors and anti-hypertensive and calcitriol treatment. In the longitudinal study, LVMI rose from 60.1±17.9 g/m2.7 to 64.2±19.3 g/m2.7 (P<0.001) and again the number of B alleles was associated with LVMI changes both in crude and in fully adjusted analyses.
These cross-sectional and longitudinal observations coherently support the hypothesis that altered Vitamin D signalling is implicated in LVH in ESRD patients.

Vitamin D receptor (VDR) gene polymorphisms and Graves' disease: a meta-analysis
http://www.ingentaconnect.com/content/bsc/cend/2009/00000070/00000006/art00018
The evidence accumulated suggested that ApaI, BsmI and FokI polymorphisms in the VDR gene were associated with susceptibility to GD in Asian populations, while ApaI, BsmI, TaqI and FokI polymorphisms were not associated with GD in Caucasian populations. Additional studies are required to allow a more definitive conclusion.

Influence of IL-6, COL1A1, and VDR gene polymorphisms on bone mineral density in Crohn’s disease
http://gut.bmj.com/content/54/11/1579.abstract

Background: Osteoporosis is an important cause of morbidity in patients with Crohn’s disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis.
Conclusion:IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn’s disease but the particular VDR gene polymorphisms studied do not have a major effect.

Vitamin D receptor gene mutation linked to chronic periodontitis.
Biotech Week | December 17, 2003
http://www.encyclopedia.com/doc/1G1-111192977.html
2003 DEC 17 - (NewsRx.com & NewsRx.net) -- A vitamin D receptor gene mutation associated with increased susceptibility to TB and HBV infection is also linked to a heighted risk of chronic periodontitis (CP).
According to published research from Japan, CP "is caused by enhanced resorption of the alveolar bone supporting the teeth and is associated with intraoral inflammation after infection with certain bacteria." "The VDR gene polymorphism was reported recently to be deeply related to the occurrence of tuberculosis and infection of chronic hepatitis B virus,"…

Vitamin D Receptor Polymorphism is Associated with Psoriasis
http://www.nature.com/jid/journal/v112/n1/full/5600393a.html

Vitamin D receptor is a trans-acting transcriptional factor that mediates 1alpha,25-dihydroxyvitamin D3 action in the regulation of target gene expression. Recent studies have shown that clinical response of psoriasis to 1alpha,25-dihydroxyvitamin D3 is correlated with the vitamin D receptor mRNA expression level, which may be influenced by the genotype of the vitamin D receptor. In this study, we have explored a possible association between psoriasis and the polymorphism in the gene encoding the vitamin D receptor. We examined the allelic frequencies of the vitamin D receptor in psoriasis patients (n = 104) and in healthy controls (n = 104) by analyzing the restriction pattern of the polymerase chain reaction products. A significant increase in the frequency of the A allele (absence of the restriction site at intron by ApaI restriction fragment length polymorphism was observed in psoriasis patients compared with that of the control group, and the tendency was more accentuated in early onset psoriasis. Odds ratios (95% confidence interval) for psoriasis of AA and Aa genotypes were 5.0 (1.3–19.1) and 2.4 (1.3–4.3), and odds ratios for early onset of AA and Aa genotypes were 6.4 (1.6–25.0) and 3.1 (1.7–5.9), respectively. Allele frequencies for A and a alleles were 0.317 and 0.683 in the psoriasis group and 0.168 and 0.832 in the control group (p = 0.001). A significant association between vitamin D receptor genotypes and the mean age at onset was observed (p < 0.05). Our findings suggest that allelic variance in the vitamin D receptor gene itself or other genes in linkage disequilibrium with this gene, could predispose to the development of psoriasis.

Spine bone mineral density and VDR polymorphism in subjects with ulcerative colitis.

http://www.biomedsearch.com/nih/Spine-bone-mineral-density-VDR/19365702.html

This study established bone mineral density in subjects with ulcerative colitis with respect to disease dissemination and severity and the association between skeletal status and vitamin D receptor (VDR) polymorphism. Forty-seven patients aged 47.6 +/- 14.8 years and 47 age- and sex-matched control subjects were evaluated. Disease duration was 8.6 +/- 7.2 years. Twenty-four subjects demonstrated mild, 17 moderate, and 5 severe forms of ulcerative colitis; local (proctitis and proctosigmoiditis) changes were present in 26 and disseminated changes in 21. Bone mineral density (BMD, g/cm(2)) was assessed at the spine, and distribution of VDR polymorphism was established. In six patients (12.8%) and in two controls (4.25%), T-score for BMD was below -2.5, but mean values of BMD did not differ between all patients and controls. Patients with moderate and severe form of disease had lower BMD measurements than patients with a mild form of colitis ulcerosa (P < 0.05), and subjects with disseminated intestinal changes had lower BMD measurements than subjects with local changes (P < 0.001). Distribution of VDR polymorphism did not differ between patients and controls. Spine Z-score was dependent on VDR polymorphism (P < 0.05) in male and female patients but not in controls. We concluded that, in patients with ulcerative colitis (UC), spine bone mineral density decreases with progression and dissemination of the disease, and that VDR polymorphism is associated with spine bone mineral density. VDR genotype bb is significantly less likely to cause low BMD in male UC patients, and VDR genotype tt is more likely to cause low BMD in female patients.

Association of Vitamin D Receptor Gene Polymorphism and
Parkinson’s Disease in Koreans

http://jkms.org/Synapse/Data/PDFData/0063JKMS/jkms-20-495.pdf

1 ,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of
vitamin D, has anti-inflammatory effects and can prevent experimental Parkinson’s
disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific
nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy
individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI
polymorphisms were markers for the susceptibility to PD in Korean patients. Each
polymorphism was detected using polymerase chain reaction (PCR)-based restriction
analysis. In addition, the relationship between the BsmI polymorphisms and
the clinical manifestations of PD was evaluated. Overexpression of the b allele
(91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was
found in the PD patients compared with the controls. These results show for the
first time an association between PD and a VDRG polymorphism, which might be
involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to
another pathogenic gene locus.

Vitamin D receptor gene polymorphisms in patients
with thyroid cancer

http://www.gtmb.org/VOL11B/INDIVIDUAL/29._Haghpanah_et_al,_299-304%201.pdf