PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms and lipid and lipoprotein levels in a Southern Brazilian population
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Cardiovascular disease is the main cause of death worldwide, and dyslipidemia is an important multifactorial risk factor. Considering the involvement of nuclear receptors in metabolic pathways, and that some of the receptors act in lipid metabolism and homeostasis, the aim of the present study was to investigate the influence of genetic variations in RXRA, PPARA, NR1I2, and NR1I3 on lipid and lipoprotein levels. Five polymorphisms in the aforementioned genes were genotyped in 622 Brazilians of European descent by PCR-RFLP or TaqMan genotyping assays. In general, carriers of the A insertion of RXRA rs11381416 polymorphism showed higher levels of triglyceride (TG; 1.80 ± 1.20 vs. 1.52 ± 1.20 mmol/L; P = 0.020). Moreover, sexual dimorphic association was found (gender*NR1I3 rs2501873 genotype interaction P < 0.001), males with NR1I3 rs2501873 G/G genotype had lower TG levels (ANCOVA, P = 0.009). Our results suggest that polymorphisms in the RXRA and NR1I3 genes influence lipid profile in a Southern Brazilian population. However, these general and gender association require confirmation in subsequent studies.
KeywordsPPARA RXRA NR1I2 NR1I3 Polymorphisms Lipid and lipoprotein levels
Financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Instituto do Milenio (CNPq, Brazil) Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil), Programa de Bolsas REUNI/UFCSPA and PROAP-CAPES. Thanks are due to Ana Lúcia S. Antunes and Maria Perpétua de O. Pinto from the Clinical Analysis Laboratory of the Pharmacy College and to Gledison Gastaldo from the Biochemical Laboratory of the Clinical Hospital of Porto Alegre. We are also grateful to André Vargas, Marsel Arsand, Fabiana M. de Andrade and Vanessa S. Mattevi for their help in sample collection.
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