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
N1 - Funding Information:
We thank Professor Ian Gibb, Dr Steve Turner, and Marie-Claude Fawcett (Royal Victoria Infirmary, Newcastle-upon-Tyne, U.K.) for carrying out the laboratory assays; and the Centre for Longitudinal studies, Institute of Education (original data producers) for providing the data. The Medical Research Council funded the 2002–2004 clinical follow-up of the 1958 birth cohort (grant G0000934). This work was undertaken at the Centre for Paediatric Epidemiology and Biostatistics which benefits from funding support from the MRC in its capacity as the MRC Centre of Epidemiology for Child Health. Research at the University College London Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. Funding for the project was provided by the British Heart Foundation (grant PG/09/023). Additional support was obtained from the UK Medical Research Council (grant G0601653) and SALVE/PREVMEDSYN with Academy of Finland. The Twins UK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Tim Spector is holder of an ERC Advanced Principal Investigator award. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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
UR - http://www.scopus.com/inward/record.url?scp=84899153203&partnerID=8YFLogxK
U2 - 10.1186/1471-2156-15-37
DO - 10.1186/1471-2156-15-37
M3 - Article
C2 - 24641809
AN - SCOPUS:84899153203
SN - 1471-2156
VL - 15
JO - BMC Genetics
JF - BMC Genetics
M1 - 37
ER -