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Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits
The KLF14 gene is a key metabolic transcriptional transregulator with monoallelic maternal expression. KLF14 variants are only associated with adipose tissue gene expression, and KLF14 promoter methylation is strongly associated with age. This study investigated whether age, sex, and obesity mediate...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032945/ https://www.ncbi.nlm.nih.gov/pubmed/35456983 http://dx.doi.org/10.3390/ijms23084165 |
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author | Wu, Semon Hsu, Lung-An Teng, Ming-Sheng Chou, Hsin-Hua Ko, Yu-Lin |
author_facet | Wu, Semon Hsu, Lung-An Teng, Ming-Sheng Chou, Hsin-Hua Ko, Yu-Lin |
author_sort | Wu, Semon |
collection | PubMed |
description | The KLF14 gene is a key metabolic transcriptional transregulator with monoallelic maternal expression. KLF14 variants are only associated with adipose tissue gene expression, and KLF14 promoter methylation is strongly associated with age. This study investigated whether age, sex, and obesity mediate the effects of KLF14 variants and DNA methylation status on body shape indices and metabolic traits. In total, the data of 78,742 and 1636 participants from the Taiwan Biobank were included in the regional plot association analysis for KLF14 variants and KLF14 methylation, respectively. Regional plot association studies revealed that the KLF14 rs4731702 variant and the nearby strong linkage disequilibrium polymorphisms were the lead variants for lipid profiles, blood pressure status, insulin resistance surrogate markers, and metabolic syndrome mainly in female participants and for body shape indices mainly in obese women. Significant age-dependent associations between KLF14 promoter methylation levels and body shape indices, and metabolic traits were also noted predominantly in female participants. KLF14 variants and KLF14 hypermethylation status were associated with metabolically healthy and unhealthy phenotypes, respectively, in obese individuals, and only the KLF14 variants demonstrated a significant association with both higher adiposity and lower cardiometabolic risk in the same allele, revealing uncoupled excessive adiposity from its cardiometabolic comorbidities, especially in obese women. Variations of KLF14 are associated with body shape indices, metabolic traits, insulin resistance, and metabolically healthy status. Differential genetic and epigenetic effects of KLF14 are age-, sex- and obesity-dependent. These results provided a personalized reference for the management of cardiometabolic diseases in precision medicine. |
format | Online Article Text |
id | pubmed-9032945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90329452022-04-23 Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits Wu, Semon Hsu, Lung-An Teng, Ming-Sheng Chou, Hsin-Hua Ko, Yu-Lin Int J Mol Sci Article The KLF14 gene is a key metabolic transcriptional transregulator with monoallelic maternal expression. KLF14 variants are only associated with adipose tissue gene expression, and KLF14 promoter methylation is strongly associated with age. This study investigated whether age, sex, and obesity mediate the effects of KLF14 variants and DNA methylation status on body shape indices and metabolic traits. In total, the data of 78,742 and 1636 participants from the Taiwan Biobank were included in the regional plot association analysis for KLF14 variants and KLF14 methylation, respectively. Regional plot association studies revealed that the KLF14 rs4731702 variant and the nearby strong linkage disequilibrium polymorphisms were the lead variants for lipid profiles, blood pressure status, insulin resistance surrogate markers, and metabolic syndrome mainly in female participants and for body shape indices mainly in obese women. Significant age-dependent associations between KLF14 promoter methylation levels and body shape indices, and metabolic traits were also noted predominantly in female participants. KLF14 variants and KLF14 hypermethylation status were associated with metabolically healthy and unhealthy phenotypes, respectively, in obese individuals, and only the KLF14 variants demonstrated a significant association with both higher adiposity and lower cardiometabolic risk in the same allele, revealing uncoupled excessive adiposity from its cardiometabolic comorbidities, especially in obese women. Variations of KLF14 are associated with body shape indices, metabolic traits, insulin resistance, and metabolically healthy status. Differential genetic and epigenetic effects of KLF14 are age-, sex- and obesity-dependent. These results provided a personalized reference for the management of cardiometabolic diseases in precision medicine. MDPI 2022-04-09 /pmc/articles/PMC9032945/ /pubmed/35456983 http://dx.doi.org/10.3390/ijms23084165 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Semon Hsu, Lung-An Teng, Ming-Sheng Chou, Hsin-Hua Ko, Yu-Lin Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title | Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title_full | Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title_fullStr | Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title_full_unstemmed | Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title_short | Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits |
title_sort | differential genetic and epigenetic effects of the klf14 gene on body shape indices and metabolic traits |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032945/ https://www.ncbi.nlm.nih.gov/pubmed/35456983 http://dx.doi.org/10.3390/ijms23084165 |
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