A vitamin D pathway gene-gene interaction affects low-density lipoprotein cholesterol levels

J Nutr Biochem. 2016 Dec:38:12-17. doi: 10.1016/j.jnutbio.2016.08.002. Epub 2016 Aug 15.

Abstract

Much evidence suggests an association between vitamin D deficiency and chronic diseases such as obesity and dyslipidemia. Although genetic factors play an important role in the etiology of these diseases, only a few studies have investigated the relationship between vitamin D-related genes and anthropometric and lipid profiles. The aim of this study was to investigate the association of three vitamin D-related genes with anthropometric and lipid parameters in 542 adult individuals. We analyzed the rs2228570 polymorphism in the vitamin D receptor gene (VDR), rs2134095 in the retinoid X receptor gamma gene (RXRG) and rs7041 in the vitamin D-binding protein gene (GC). Polymorphisms were genotyped by TaqMan allelic discrimination. Gene-gene interactions were evaluated by the general linear model. The functionality of the polymorphisms was investigated using the following predictors and databases: SIFT (Sorting Intolerant from Tolerant), PolyPhen-2 (Polymorphism Phenotyping v2) and Human Splicing Finder 3. We identified a significant effect of the interaction between RXRG (rs2134095) and GC (rs7041) on low-density lipoprotein cholesterol (LDL-c) levels (P=.005). Furthermore, our in silico analysis suggested a functional role for both variants in the regulation of the gene products. Our results suggest that the vitamin D-related genes RXRG and GC affect LDL-c levels. These findings are in agreement with other studies that consistently associate vitamin D and lipid profile. Together, our results corroborate the idea that analyzing gene-gene interaction would be helpful to clarify the genetic component of lipid profile.

Keywords: Gene–gene interaction; Lipid profile; Polymorphisms; Retinoid X receptor; Vitamin D receptor; Vitamin D-binding protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Brazil
  • Cholesterol, LDL / blood*
  • Computational Biology
  • Databases, Genetic
  • Expert Systems
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / genetics*
  • Hypercholesterolemia / metabolism
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism
  • Retinoid X Receptor gamma / genetics*
  • Retinoid X Receptor gamma / metabolism
  • Vitamin D-Binding Protein / genetics*
  • Vitamin D-Binding Protein / metabolism
  • Young Adult

Substances

  • Cholesterol, LDL
  • Receptors, Calcitriol
  • Retinoid X Receptor gamma
  • VDR protein, human
  • Vitamin D-Binding Protein