Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits
Background Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor,...
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ftimperialcol:oai:spiral.imperial.ac.uk:10044/1/85656 2023-05-15T17:42:55+02:00 Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits Vimaleswaran, KS Cavadino, A Berry, DJ Mangino, M Andrews, P Moore, JH Spector, TD Power, C Jaervelin, M-R Hyppoenen, E 2014-03-10 http://hdl.handle.net/10044/1/85656 https://doi.org/10.1186/1471-2156-15-37 English eng BioMed Central BMC Genetics 1471-2156 http://hdl.handle.net/10044/1/85656 doi:10.1186/1471-2156-15-37 © 2014 Vimaleswaran et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. http://creativecommons.org/licenses/by/2.0 CC0 PDM CC-BY 8 1 Science & Technology Life Sciences & Biomedicine Genetics & Heredity VDR RXRG SNPs SNP-SNP interaction 1958BC 25-HYDROXYVITAMIN D BLOOD-PRESSURE RISK POLYMORPHISMS ASSOCIATION METAANALYSIS AGE COHORT LOCI LIFE Alleles Blood Pressure Body Mass Index Cholesterol HDL LDL Cohort Studies Finland Glycated Hemoglobin A Humans Likelihood Functions Models Genetic Polymorphism Single Nucleotide Receptors Calcitriol Retinoid X Receptors Triglycerides Twin Studies as Topic United Kingdom Waist Circumference Waist-Hip Ratio 0604 Genetics Journal Article 2014 ftimperialcol https://doi.org/10.1186/1471-2156-15-37 2021-01-28T23:39:17Z Background Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. Results After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (Pinteraction >0.17). Conclusions Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings. Article in Journal/Newspaper Northern Finland Imperial College London: Spiral BMC Genetics 15 1 37 |
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Open Polar |
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Imperial College London: Spiral |
op_collection_id |
ftimperialcol |
language |
English |
topic |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity VDR RXRG SNPs SNP-SNP interaction 1958BC 25-HYDROXYVITAMIN D BLOOD-PRESSURE RISK POLYMORPHISMS ASSOCIATION METAANALYSIS AGE COHORT LOCI LIFE Alleles Blood Pressure Body Mass Index Cholesterol HDL LDL Cohort Studies Finland Glycated Hemoglobin A Humans Likelihood Functions Models Genetic Polymorphism Single Nucleotide Receptors Calcitriol Retinoid X Receptors Triglycerides Twin Studies as Topic United Kingdom Waist Circumference Waist-Hip Ratio 0604 Genetics |
spellingShingle |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity VDR RXRG SNPs SNP-SNP interaction 1958BC 25-HYDROXYVITAMIN D BLOOD-PRESSURE RISK POLYMORPHISMS ASSOCIATION METAANALYSIS AGE COHORT LOCI LIFE Alleles Blood Pressure Body Mass Index Cholesterol HDL LDL Cohort Studies Finland Glycated Hemoglobin A Humans Likelihood Functions Models Genetic Polymorphism Single Nucleotide Receptors Calcitriol Retinoid X Receptors Triglycerides Twin Studies as Topic United Kingdom Waist Circumference Waist-Hip Ratio 0604 Genetics Vimaleswaran, KS Cavadino, A Berry, DJ Mangino, M Andrews, P Moore, JH Spector, TD Power, C Jaervelin, M-R Hyppoenen, E Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
topic_facet |
Science & Technology Life Sciences & Biomedicine Genetics & Heredity VDR RXRG SNPs SNP-SNP interaction 1958BC 25-HYDROXYVITAMIN D BLOOD-PRESSURE RISK POLYMORPHISMS ASSOCIATION METAANALYSIS AGE COHORT LOCI LIFE Alleles Blood Pressure Body Mass Index Cholesterol HDL LDL Cohort Studies Finland Glycated Hemoglobin A Humans Likelihood Functions Models Genetic Polymorphism Single Nucleotide Receptors Calcitriol Retinoid X Receptors Triglycerides Twin Studies as Topic United Kingdom Waist Circumference Waist-Hip Ratio 0604 Genetics |
description |
Background Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. Results After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (Pinteraction >0.17). Conclusions Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings. |
format |
Article in Journal/Newspaper |
author |
Vimaleswaran, KS Cavadino, A Berry, DJ Mangino, M Andrews, P Moore, JH Spector, TD Power, C Jaervelin, M-R Hyppoenen, E |
author_facet |
Vimaleswaran, KS Cavadino, A Berry, DJ Mangino, M Andrews, P Moore, JH Spector, TD Power, C Jaervelin, M-R Hyppoenen, E |
author_sort |
Vimaleswaran, KS |
title |
Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
title_short |
Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
title_full |
Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
title_fullStr |
Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
title_full_unstemmed |
Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits |
title_sort |
interaction between allelic variations in vitamin d receptor and retinoid x receptor genes on metabolic traits |
publisher |
BioMed Central |
publishDate |
2014 |
url |
http://hdl.handle.net/10044/1/85656 https://doi.org/10.1186/1471-2156-15-37 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
8 1 |
op_relation |
BMC Genetics 1471-2156 http://hdl.handle.net/10044/1/85656 doi:10.1186/1471-2156-15-37 |
op_rights |
© 2014 Vimaleswaran et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. http://creativecommons.org/licenses/by/2.0 |
op_rightsnorm |
CC0 PDM CC-BY |
op_doi |
https://doi.org/10.1186/1471-2156-15-37 |
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BMC Genetics |
container_volume |
15 |
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37 |
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1766144854616702976 |