Influence of vitamin D receptor gene polymorphisms on mortality risk in hemodialysis patients

Marco, Maria Paz; Craver, Lourdes; Betriu, Àngels; Fibla, Joan; Fernàndez, Elvira

doi:10.1053/ajkd.2001.28582

Cited by 54 publications

(50 citation statements)

References 33 publications

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“…One of the first reports on this subject was by Teng et al (119), who showed improved survival in patients treated with paricalcitol compared with those treated with calcitriol. The findings that VDRA supplementation is associated with better survival (54,70,76,80,105,120,121,129) and that elevated Ca and P levels are associated with a higher risk of mortality in dialysis patients (10 -12) support the hypothesis that the less calcemic and phosphatemic VDRAs may be advantageous for CKD patients.…”

Section: Potential New Uses Of Vdra On Renal Patientsmentioning

confidence: 80%

A new role for vitamin D receptor activation in chronic kidney disease

Valdivielso

Cannata-Andía

Coll

et al. 2009

American Journal of Physiology-Renal Physiology

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Valdivielso JM, Cannata-Andía J, Coll B, Fernández E. A new role for vitamin D receptor activation in chronic kidney disease. Am J Physiol Renal Physiol 297: F1502-F1509, 2009. First published July 22, 2009 doi:10.1152/ajprenal.00130.2009.-Vitamin D has proven to be much more than a simple "calcium hormone." The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called "sunshine hormone." In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyperparathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism.VITAMIN D IS A STEROID HORMONE that has long been known for its important role in regulating body levels of calcium (Ca) and phosphorus (P) and in mineralization of bone. However, there is an increasing amount of data proving that vitamin D exerts its effects beyond kidney, intestine, and bone (Fig. 1). The active form of vitamin D (calcitriol) mediates its biological effects by binding to the vitamin D receptor (VDR), which then translocates to the nuclei of target cells (for review, see Ref. 47). The VDR is a ligand-activated transcription factor that, after activation, recruits cofactor molecules and binds to specific DNA binding sites to modify the expression of target genes. Ligand-mediated conformational changes of the VDR contribute to specific mechanisms in its signaling cascade. Thus the structural chemical modification of active vitamin D is a powerful tool in discovering new compounds that show selective activation of the VDR. Over the last years, a number of new VDR activators (VDRAs), defined as compounds that can bind to VDR and induce its activation, have been synthesized and used in several diseases, including in patients with CKD. Their potential as new therapeutic agents has boosted this area of research. Moreover, new evidence suggests that VDR polymorphisms may influence the response to VDRAs (125). Present Use of VDRAs in Patients with CKDOne of the main complications in patients with CKD is the development of secondary hyperparathyroidism (sHPT). In the past, the increase in parathyroid gland (PTG) size and parathyroid hormone (PTH) synthesis were attributed to a decrease in circulating Ca. As a result, patients with sHPT were treated with oral vitamin D metabolites to correct ...

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Section: Potential New Uses Of Vdra On Renal Patientsmentioning

confidence: 80%

A new role for vitamin D receptor activation in chronic kidney disease

Valdivielso

Cannata-Andía

Coll

et al. 2009

American Journal of Physiology-Renal Physiology

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“…Further work is needed to define the mechanisms by which such variations in VDR synthesis lead to variation in cellular function and to determine whether such variation is abolished by adequate vitamin D repletion. The prescient suggestion, made 25 years ago, that requirements for vitamin D may vary between individuals (52) is now supported by clinical findings in tuberculosis, uremia, and colonic adenoma (16,30,53,54). It is clear that susceptibility to a wide range of disorders associated with VDR polymorphism, including type 1 and type 2 diabetes, could be reduced if adequacy of vitamin D repletion could be redefined to include those with the highest requirements (6 -8,19,20,55).…”

Section: Discussionmentioning

confidence: 97%

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

et al. 2002

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Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific microimmunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n ‫؍‬ 143, P < 0.0001) gave age (P ‫؍‬ 0.002), TaqI (P < 0.0001), and BMI (P ‫؍‬ 0.001) as independent determinants; with the inclusion of VDR mRNA and VDR protein levels, VDR mRNA was the sole independent determinant (n ‫؍‬ 41, P ‫؍‬ 0.024). However, the best-fit model for VDR mRNA (P ‫؍‬ 0.004) gave FokI (P ‫؍‬ 0.044) and TaqI (P ‫؍‬ 0.04) genotypes and insulin secretory capacity (P ‫؍‬ 0.042) as independent determinants. For VDR protein levels, the best-fit model (P ‫؍‬ 0.006) gave TaqI genotype (P ‫؍‬ 0.005) and circulating 1,25-dihydroxyvitamin-D levels (P ‫؍‬ 0.03) as independent determinants. In conclusion, these studies confirm an association between VDR polymorphisms and insulin secretory capacity and demonstrate the VDR genotype to be a significant determinant of VDR mRNA and VDR protein levels in PBMCs, providing functional support to previously described genetic associations with the VDR gene. Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity. Because the VDR is expressed in a large number of tissues, it is not surprising that ligand-activated VDR modulates the expression of many genes. The VDR gene, located on chromosome 12q, has 14 exons, 6 of which are in the 5Ј untranslated region (1a-1f). At least 22 unique nonfunctional VDR variants have been described, most of which lead to rare syndromes associated with vitamin D-resistant rickets (4). A number of common chronic disorders of inflammatory, infective, and autoimmune etiologies, including both type 1 and type 2 diabetes and colorectal adenoma, have been shown to be associated with specific polymorphisms of the vitamin D receptor gene, although not all such associ-

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“…The BsmI-ApaI-TaqI haplotype 1 (baT) was associated with a positive effect on cognitive function and depressive symptoms (17). In hemodialysis patients, the BsmI b allele, which is part of haplotype 1, was related to increased survival (37). In addition, the b allele is associated with a lower prevalence of coronary artery disease and diabetes mellitus type 2 (12,13).…”

Section: Discussionmentioning

confidence: 99%

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Jongh

Lips

Rijs

et al. 2011

European Journal of Endocrinology

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Context: Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality. Objective: To investigate the associations between VDR gene variants and mortality among older people. Design: The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (R65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms. Results: During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2-GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copiesZreference, HR, 95% CI: 1 copy 2.01, 0.99-4.07 and 2 copies 1.81, 0.87-4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2-GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83-1.41).

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Influence of vitamin D receptor gene polymorphisms on mortality risk in hemodialysis patients

Cited by 54 publications

References 33 publications

A new role for vitamin D receptor activation in chronic kidney disease

A new role for vitamin D receptor activation in chronic kidney disease

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

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