Vitamin D Receptor Gene Polymorphism and Left Ventricular Hypertrophy in Chronic Kidney Disease

Domenico Santoro,Daniela Caccamo,Angela Alibrandi,Michele Buemi,Vincenzo Savica,Giorgia Gagliostro,Riccardo Ientile,Guido Bellinghieri

doi:10.3390/nu6031029

Domenico Santoro, Daniela Caccamo + Show 6 more

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https://doi.org/10.3390/nu6031029

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Journal: Nutrients	Publication Date: Mar 10, 2014
Citations: 56	License type: CC BY 4.0

Affiliation: University of Messina

Abstract

FokI and BsmI polymorphisms of vitamin D receptor (VDR) gene are regarded as reliable markers of disturbed vitamin D signaling pathway. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD) patients. Since BsmI polymorphism has been associated with LVH in ESRD patients, we addressed this study in patients with chronic kidney disease (CKD) not yet on dialysis. One hundred and forty five patients with CKD stage 3 were genotyped for FokI and BsmI VDR polymorphisms, in order to assess the relationships between these VDR polymorphisms, some markers of mineral bone disorders, and LVH measured by echocardiography. Patients bearing either the Ff heterozygous or FF homozygous genotype had significantly higher PTH values than those bearing the ff genotype. The relationships between VDR genotypes and LVH revealed a highly significant association of the BsmI Bb heterozygous genotype with LVH. In patients with CKD stage 3 BsmI B allele was independently related to LVH. Since LVH is a frequent finding in dialysis population due to several mechanisms, the presence of the same relationship in patients with CKD strengthens the hypothesis that alterations of vitamin D signaling are implicated in LVH development in patients with renal diseases.

Highlights

Several studies indicate a relationship between vitamin D, survival, vascular calcification and inflammation [1,2,3]
Since changes in left ventricle mass (LVM) are very frequent in hemodialysis (HD) patients and may be related to both pressure overload and several hemodynamic as well as non-hemodynamic factors [10], we aimed to evaluate the effects of alterations in vitamin D receptor (VDR) signaling in a population of patients with chronic kidney disease (CKD) not yet on dialysis
We investigated the association between either VDR FokI or BsmI polymorphim with co-morbidities observed in CKD patients, i.e., diabetes, hypertension, and Left ventricular hypertrophy (LVH)

Summary

Introduction

Several studies indicate a relationship between vitamin D, survival, vascular calcification and inflammation [1,2,3]. In addition to its central role in the regulation of bone mineral metabolism, vitamin D is involved in the regulation of other systems, including the immune, cardiovascular and endocrine. The biological activity of vitamin D is mediated by the activation of the high-affinity nuclear vitamin D receptor (VDR) [4]. VDR is a ligand-dependent transcription factor, belonging to the steroid nuclear receptor gene family, that, after activation, heterodimerizes with retinoid X receptor and binds to specific DNA sites to modify the expression of target genes [5,6]. If not all, pleiotropic actions of vitamin D and its analogues are mediated by VDR. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD)

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