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

Abstract

BackgroundLow 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.ResultsAfter 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).ConclusionsOur 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.

Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene (VDR) May Have an Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations of AP Patients and Alcohol-Abuse Controls

“…It would, therefore, be of value to analyze also the retinoid-X receptor ( RXR ) gene for the occurrence of SNPs. However, so far, a polymorphism in the RXR gene was only found in hyperlipidemia and type 2 diabetes [ 65 ]. In addition, we could not extensively compare vitamin D plasma concentrations in controls and AP groups because of their different lifestyles, including diet, sun exposure, and vitamin D supplementation.…”

Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3

“…Body fat mass [25–28], trunk fat [26, 29], WC, waist to hip ratio (WHR) [26, 28, 30] and serum lipids [22, 31] have been reported to be negatively associated with the changes in circulating 25(OH)D levels following vitamin D supplementation in some, but not all studies [30, 32–36]. In addition, studies investigating the association of genetic polymorphisms and haplotypes of VDR with adiposity and metabolic measures have shown equivocal results [8, 12, 37–43]. Nevertheless, without considering both VDR genotypes, vitamin D intake and circulating 25(OH) D data simultaneously, we could not determine the complex interplay between genetic variation in the VDR gen, and vitamin D with obesity or metabolic syndrome.…”

Reduced telomere length is associated with fibrotic joint disease suggesting that impaired telomere repair contributes to joint fibrosis

“…Adjustment was made for age, sex, BMI and smoking status. The cluster option in Stata was used to adjust for family relatedness (as previously described [ 12 – 14 ]. This model provides a robust estimation of the standard errors taking into account that the observations within families are not independent.…”