title: Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits.
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 (P(interaction) >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.
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK. v.karani@reading.ac.uk.
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Alana
authors.initials: A
authors.lastname: Cavadino
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Berry
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Peter
authors.initials: P
authors.lastname: Andrews
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
mesh_terms: D000483:Alleles; D001794:Blood Pressure; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005387:Finland; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D047488:Retinoid X Receptors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D018433:Twin Studies as Topic; D006113:United Kingdom; D055105:Waist Circumference; D049629:Waist-Hip Ratio
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014280:Triglycerides