Full metadata record
DC Field | Value | Language |
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dc.creator | Garcia-Calzon, S. (Sonia) | - |
dc.creator | Perfilyev, A. (Alexander) | - |
dc.creator | Mello, V.D. (Vanessa D.) de | - |
dc.creator | Pihlajamäki, J. (Jussi) | - |
dc.creator | Ling, C. (Charlotte) | - |
dc.date.accessioned | 2024-01-24T13:10:51Z | - |
dc.date.available | 2024-01-24T13:10:51Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Garcia-Calzon, S. (Sonia); Perfilyev, A. (Alexander); Mello, V.D. (Vanessa D.) de; et al. "Sex differences in the methylome and transcriptome of the human liver and circulating HDL-cholesterol levels". The Journal of Clinical Endocrinology & Metabolism. 103 (12), 2018, 4395 - 4408 | es_ES |
dc.identifier.issn | 0021-972X | - |
dc.identifier.uri | https://hdl.handle.net/10171/68510 | - |
dc.description.abstract | Context: Epigenetics may contribute to sex-specific differences in human liver metabolism. Objective: To study the impact of sex on DNA methylation and gene expression in human liver. Design/setting: Cross-sectional, Kuopio Obesity Surgery Study. Participants/intervention: We analyzed DNA methylation with the Infinium HumanMethylation450 BeadChip in liver of an obese population (34 males, 61 females). Females had a higher high-density lipoprotein (HDL)-cholesterol levels compared with males. Gene expression was measured with the HumanHT-12 Expression BeadChip in a subset of 42 participants. Results: Females displayed higher average methylation in the X-chromosome, whereas males presented higher methylation in autosomes. We found 9455 CpG sites in the X-chromosome and 33,205 sites in autosomes with significant methylation differences in liver between sexes (q < 0.05). When comparing our findings with published studies, 95% of the sex-specific differences in liver methylation in the X-chromosome were also found in pancreatic islets and brain, and 26 autosomal sites showed sex-specific methylation differences in the liver as well as in other human tissues. Furthermore, this sex-specific methylation profile in liver was associated with hepatic gene expression changes between males and females. Notably, females showed higher HDL-cholesterol levels, which were associated with higher KDM6A expression and epigenetic differences in human liver. Accordingly, silencing of KDM6A in cultured liver cells reduced HDL-cholesterol levels and APOA1 expression, which is a major component of HDL particles. Conclusions: Human liver has a sex-specific methylation profile in both the X-chromosome and autosomes, which associates with hepatic gene expression changes and HDL-cholesterol. We identified KDM6A as a novel target that regulates HDL-cholesterol levels. | es_ES |
dc.description.sponsorship | This work has been supported by grants fromthe SwedishResearchCouncil (toC.L.),Region Sk ˚ane(ALF; to C.L.), Knut and Alice Wallenberg Foundation (to C.L.), EFSD/ Lilly (to C.L.), The Swedish Diabetes Foundation, P ˚ahlsson Foundation (to C.L.), EXODIAB (to C.L.), Linn´e grant (B31 5631/2006), the Swedish Foundation for Strategic Research Dnr IRC15-0067 (to C.L.), and Academy of Finland (138006) and Kuopio University Hospital Project grant (EVO/VTR to J.P.). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant 706081 (EpiHope; to S.G.-C. and C.L.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/706081/EU | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Materias Investigacion::Ciencias de la Salud | es_ES |
dc.subject | Sex differences | es_ES |
dc.subject | Liver | es_ES |
dc.subject | Cholesterol levels | es_ES |
dc.title | Sex differences in the methylome and transcriptome of the human liver and circulating HDL-cholesterol levels | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.note | This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.identifier.doi | 10.1210/jc.2018-00423 | - |
dadun.citation.endingPage | 4408 | es_ES |
dadun.citation.number | 12 | es_ES |
dadun.citation.publicationName | The Journal of Clinical Endocrinology & Metabolism | es_ES |
dadun.citation.startingPage | 4395 | es_ES |
dadun.citation.volume | 103 | es_ES |
dc.identifier.pmid | 29846646 | - |
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