Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits

Karani S. Vimaleswaran, Alana Cavadino, Diane J. Berry, Massimo Mangino, Peter Andrews, Jason H. Moore, Timothy D. Spector, Chris Power, Marjo Riitta Järvelin, Elina Hyppönen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

LanguageEnglish
Article number37
JournalBMC Genetics
Volume15
DOIs
Publication statusPublished - 19 Mar 2014

Keywords

  • 1958BC
  • RXRG
  • SNP-SNP interaction
  • SNPs
  • VDR

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Vimaleswaran, Karani S. ; Cavadino, Alana ; Berry, Diane J. ; Mangino, Massimo ; Andrews, Peter ; Moore, Jason H. ; Spector, Timothy D. ; Power, Chris ; Järvelin, Marjo Riitta ; Hyppönen, Elina. / Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits. In: BMC Genetics. 2014 ; Vol. 15.
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abstract = "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.",
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Vimaleswaran, KS, Cavadino, A, Berry, DJ, Mangino, M, Andrews, P, Moore, JH, Spector, TD, Power, C, Järvelin, MR & Hyppönen, E 2014, 'Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits', BMC Genetics, vol. 15, 37. https://doi.org/10.1186/1471-2156-15-37

Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits. / Vimaleswaran, Karani S.; Cavadino, Alana; Berry, Diane J.; Mangino, Massimo; Andrews, Peter; Moore, Jason H.; Spector, Timothy D.; Power, Chris; Järvelin, Marjo Riitta; Hyppönen, Elina.

In: BMC Genetics, Vol. 15, 37, 19.03.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits

AU - Vimaleswaran, Karani S.

AU - Cavadino, Alana

AU - Berry, Diane J.

AU - Mangino, Massimo

AU - Andrews, Peter

AU - Moore, Jason H.

AU - Spector, Timothy D.

AU - Power, Chris

AU - Järvelin, Marjo Riitta

AU - Hyppönen, Elina

PY - 2014/3/19

Y1 - 2014/3/19

N2 - 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.

AB - 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.

KW - 1958BC

KW - RXRG

KW - SNP-SNP interaction

KW - SNPs

KW - VDR

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U2 - 10.1186/1471-2156-15-37

DO - 10.1186/1471-2156-15-37

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JO - BMC Genetics

T2 - BMC Genetics

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