Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children

Abstract Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with...

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Main Authors: Claudia Vales-Villamarín, Olaya de Dios, Ignacio Mahíllo-Fernández, Macarena Perales, Iris Pérez-Nadador, Teresa Gavela-Pérez, Leandro Soriano-Guillén, Carmen Garcés
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-49506-2
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author Claudia Vales-Villamarín
Olaya de Dios
Ignacio Mahíllo-Fernández
Macarena Perales
Iris Pérez-Nadador
Teresa Gavela-Pérez
Leandro Soriano-Guillén
Carmen Garcés
author_facet Claudia Vales-Villamarín
Olaya de Dios
Ignacio Mahíllo-Fernández
Macarena Perales
Iris Pérez-Nadador
Teresa Gavela-Pérez
Leandro Soriano-Guillén
Carmen Garcés
author_sort Claudia Vales-Villamarín
collection DOAJ
description Abstract Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6–8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.
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spelling doaj.art-22d9d1f001244e91b2b579bc0707994b2023-12-17T12:14:27ZengNature PortfolioScientific Reports2045-23222023-12-011311710.1038/s41598-023-49506-2Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in childrenClaudia Vales-Villamarín0Olaya de Dios1Ignacio Mahíllo-Fernández2Macarena Perales3Iris Pérez-Nadador4Teresa Gavela-Pérez5Leandro Soriano-Guillén6Carmen Garcés7Lipid Research Laboratory, IIS-Fundación Jiménez DíazLipid Research Laboratory, IIS-Fundación Jiménez DíazDepartment of Biostatistics and Epidemiology, IIS-Fundación Jiménez Díaz UAMLipid Research Laboratory, IIS-Fundación Jiménez DíazLipid Research Laboratory, IIS-Fundación Jiménez DíazDepartment of Pediatrics, IIS-Fundación Jiménez DíazDepartment of Pediatrics, IIS-Fundación Jiménez DíazLipid Research Laboratory, IIS-Fundación Jiménez DíazAbstract Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6–8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.https://doi.org/10.1038/s41598-023-49506-2
spellingShingle Claudia Vales-Villamarín
Olaya de Dios
Ignacio Mahíllo-Fernández
Macarena Perales
Iris Pérez-Nadador
Teresa Gavela-Pérez
Leandro Soriano-Guillén
Carmen Garcés
Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
Scientific Reports
title Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
title_full Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
title_fullStr Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
title_full_unstemmed Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
title_short Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children
title_sort sex dependent relationship of polymorphisms in clock and rev erbα genes with body mass index and lipid levels in children
url https://doi.org/10.1038/s41598-023-49506-2
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