Group items tagged

BACKGROUND: To determine the effect of vitamin D binding protein (DBP) genotypes on 25-hydroxyvitamin D [25(OH)D] changes with vitamin D supplements, we studied 98 adults receiving 600 or 4000 IU/d vitamin D(3) for one year. METHODS: The DBP functional variant, T436K, was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Mean 25(OH)D increases were 97% for TT (n=48), 151% for TK (n=31) and 307% (n=6) for KK genotypes (p=.004). CONCLUSIONS: As with baseline 25(OH)D, T436K genotype predicts 25(OH)D changes after long-term vitamin D supplementation. Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation. Fu L, Yun F, Oczak M, Wong BY, Vieth R, Cole DE. Clin Biochem. 2009 Jul;42(10-11):1174-7. Epub 2009 Mar 18. PMID: 19302999

Why is it that vitamin D deficiency can manifest in so many different ways in different people? One big reason is something called vitamin D receptor (VDR) genotypes, the variation in the receptor for vitamin D. Why is it that the dose of vitamin D necessary to reach a specific level differs so widely from one person to the next? VDR genotype, again. Variation in blood levels of 25-hydroxy vitamin D from a specific dose of vitamin D can vary three-fold, as shown by a University of Toronto study. In other words, a dose of 4000 units per day may yield a 25-hydroxy vitamin D blood level of 30 ng/ml in Mary, 60 ng/ml in Paul, and 90 ng/ml in Pete--same dose, different blood levels

Low vitamin D serum level is related to severe fibrosis and low responsiveness to IFN-based therapy in genotype 1 chronic hepatitis C Salvatore Petta et al. Hepatology, Volume 9999 Issue 999A, Page NA. Published Online: 4 Dec 2009 DOI: 10.1002/hep.23489 Conclusions: G1 CHC patients had low 25(OH)D serum levels, possibly due to reduced CYP27A1 expression. Low vitamin D is linked to severe fibrosis and low SVR on IFN-based therapy. (HEPATOLOGY 2010.)

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Ann N Y Acad Sci. 2009 Sep;1173:515-20. PMID: 19758194 DOI: 10.1111/j.1749-6632.2009.04656.x Discussion: We found no association of the Apal and Taql VDR gene SNPs with MS or with vitamin D metabolism in our population. Further research should assess the complex interaction between vitamin D, the VDR, and susceptibility to MS.

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Köstner K, Denzer N, Müller CS, Klein R, Tilgen W, Reichrath J. Anticancer Res. 2009 Sep;29(9):3511-36. Review. PMID: 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: association with Crohn's disease susceptibility.\nSimmons JD, Mullighan C, Welsh KI, Jewell DP.\nGut. 2000 Aug;47(2):211-4.\nPMID: 10896912 \ndoi:10.1136/gut.47.2.211

Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16. Epub 2007 Oct 25. PMID: 17962355 These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Diabetes Obes Metab. 2008 Mar;10(3):185-97. Review. PMID: 18269634 DOI: 10.1111/j.1463-1326.2007.00710.x Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus.

In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. Hirai M, Suzuki S, Hinokio Y, Hirai A, Chiba M, Akai H, Suzuki C, Toyota T. J Clin Endocrinol Metab. 2000 May;85(5):1951-3. PMID: 10843180

Our results of an association with the Fok1 VDR polymorphism further support a role of the vitamin D pathway in ovarian carcinogenesis. Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies. Tworoger SS, Gates MA, Lee IM, Buring JE, Titus-Ernstoff L, Cramer D, Hankinson SE. Cancer Res. 2009 Mar 1;69(5):1885-91. Epub 2009 Feb 17. Erratum in: Cancer Res. 2009 Jun 15;69(12):5267. Gate, Margaret A [corrected to Gates, Margaret A]. PMID: 19223536 doi: 10.1158/0008-5472.CAN-08-3515

Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Raimondi S, Johansson H, Maisonneuve P, Gandini S. Carcinogenesis. 2009 Jul;30(7):1170-80. Epub 2009 Apr 29. Review. PMID: 19403841

Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH, Badenhoop K. Diabetes. 2000 Mar;49(3):504-7. PubMed PMID: 10868975. doi: 10.2337/diabetes.49.3.504

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Chang TJ, Lei HH, Yeh JI, Chiu KC, Lee KC, Chen MC, Tai TY, Chuang LM. Clin Endocrinol (Oxf). 2000 May;52(5):575-80. PMID: 10792336 DOI: 10.1046/j.1365-2265.2000.00985.x CONCLUSIONS Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 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. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.