Vitamin D-binding protein and vitamin D receptor genotypes and 25-hydroxyvitamin D levels are associated with development of aortic and mitral valve calcification and coronary artery diseases

Mol Biol Rep. 2019 Oct;46(5):5225-5236. doi: 10.1007/s11033-019-04979-1. Epub 2019 Jul 29.

Abstract

To assess the association between vitamin D-Binding Protein (VDBP rs7041T>G) and vitamin D receptor (VDR rs1544410G>A) gene polymorphisms with susceptibility to cardiovascular diseases in population from west of Iran. Two hundred forty-nine individuals with cardiovascular disease (92 with aortic and Mitral Valves Calcification (AMVC) and 157 with Coronary Artery Diseases (CAD) that their diseases were confirmed by echocardiography and angiography and unrelated 182 healthy controls (gender and age-matched) were selected for this case-control study. The VDR 1544410G>A, and VDBP 7041T>G genotyping were detected by PCR-RFLP, serum vitamin D and lipid concentrations were measured by ELISA and enzyme assay, respectively. The VDR rs1544410G>A gene is a strong risk factor for CAD (OR = 1.28, p = 0.002) and the dominant genotype (T/G+G/G) of VDBP 7041 T>G SNP plays a protective role (OR = 0.67, p = 0.003) in AMVC development in studied population. In addition, lower level of vitamin D strongly increased the risk of CAD (15 ± 11.02 vs. 21.3 ± 18 μg/L, p = 0.043) and AMVC (12.1 ± 13.1 vs.21.3 ± 18 μg/L, p = 0.014) development in individuals carrying T/T genotype of VDBP 7041 T>G gene polymorphism. There was a strong interaction between A allele VDR rs1544410 and G allele of VDBP rs7041 genes in a protective role (OR = 0.74, p = 0.044) in AMVC patients). CAD and AMVC patients were deficient in vitamin D, i.e. their level of vitamin D was strongly lower than that in the control group. Our findings for the first time indicated that there is a strong association between vitamin D deficiency, lipid profile and the VDR rs1544410G>A and rs7T41>G VDBP genes polymorphisms. These interactions may be one of the important factors for CAD and AMVC incidence.

Keywords: Aortic and mitral valves calcification (AMVC); Coronary artery disease (CAD); Vitamin D; Vitamin D receptor (VDR) gene; Vitamin D-binding protein (VDBP) gene.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / pathology
  • Calcinosis / blood
  • Calcinosis / diagnostic imaging
  • Calcinosis / genetics*
  • Case-Control Studies
  • Coronary Angiography
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / genetics*
  • Echocardiography
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mitral Valve / diagnostic imaging
  • Mitral Valve / pathology
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics*
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D-Binding Protein / genetics*

Substances

  • GC protein, human
  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D