title: A vitamin D pathway gene-gene interaction affects low-density lipoprotein cholesterol levels.
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.
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil.
authors.forename: Nathália
authors.initials: N
authors.lastname: Grave
authors.affiliation: Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, 96020-220, Pelotas, RS, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tovo-Rodrigues
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil.
authors.forename: Janaína
authors.initials: J
authors.lastname: da Silveira
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Diego Luiz
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil.
authors.forename: Simone Morelo
authors.initials: SM
authors.lastname: Dal Bosco
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil; Setor de Genética e Biologia Molecular do Museu de Ciências Naturais, Centro de Ciências Biológicas e da Saúde, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil.
authors.forename: Verônica
authors.initials: V
authors.lastname: Contini
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Centro Universitário UNIVATES, 95900-000, Lajeado, RS, Brazil; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre, 90050-170, Porto Alegre, RS, Brazil. Electronic address: juliag@ufcspa.edu.br.
authors.forename: Júlia Pasqualini
authors.initials: JP
authors.lastname: Genro
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001938:Brazil; D008078:Cholesterol, LDL / Q000097:blood*; D019295:Computational Biology; D030541:Databases, Genetic; D005103:Expert Systems; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D047491:Retinoid X Receptor gamma / Q000235:genetics* / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D018167:Receptors, Calcitriol; D047491:Retinoid X Receptor gamma; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein
keywords: Gene–gene interaction; Lipid profile; Polymorphisms; Retinoid X receptor; Vitamin D receptor; Vitamin D-binding protein