RESUMO
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.
Assuntos
LDL-Colesterol/sangue , Predisposição Genética para Doença , Hipercolesterolemia/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Receptor X Retinoide gama/genética , Proteína de Ligação a Vitamina D/genética , Adolescente , Adulto , Alelos , Brasil , Biologia Computacional , Bases de Dados Genéticas , Sistemas Inteligentes , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Masculino , Receptores de Calcitriol/metabolismo , Receptor X Retinoide gama/metabolismo , Proteína de Ligação a Vitamina D/metabolismo , Adulto JovemRESUMO
The HLA A, B, and DRB1 allele, phenotype, and haplotype frequencies were studied in a sample of 5,000 volunteer bone marrow donors registered at the Brazilian Volunteer Bone Marrow Donor Registry. The participants live in the state of Rio Grande do Sul and were classified according to ethnic group (4,428 Caucasians, 324 mestizos [mixed race], and 248 blacks). Typing was performed using the polymerase chain reaction sequence-specific oligonucleotide method combined with Luminex technology. Twenty-one HLA-A, 33 HLA-B, and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each locus were A*02, B*35, and DRB1*13. The most frequent haplotypes were A*01 B*08 DRB1*03 in Caucasians and mestizos and A*02 B*15 and DRB1*04 in blacks. The allele frequencies were compared with samples from different Brazilian regions. In most comparisons no significant differences were found. The most significant differences were observed in the comparison of the groups of our sample, indicating that human leukocyte antigen (HLA) is a good marker to distinguish among people from different ethnic groups. The data provide insight on the knowledge of HLA diversity in the population of Rio Grande do Sul and in the search for a better match for transplant.
