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

BMC Genetics

Elina Hyppönen⁶  Marjo-Riitta Järvelin¹  Chris Power³  Timothy D Spector⁴  Jason H Moore²  Peter Andrews²  Massimo Mangino⁴  Diane J Berry³  Alana Cavadino³  Karani S Vimaleswaran⁵ 

[1] Department of Children, Young People and Families, National Institute for Health and Welfare, Box 310, 90101 Oulu, Finland;Institute for Quantitative Biomedical Sciences, Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03756, USA;Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK;Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK;Hugh Sinclair Unit of Human Nutrition, Department of Food & Nutritional Sciences, School of Chemistry, Food & Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UK;School of Population Health and Sansom Institute, University of South Australia; South Australian Health and Medical Research Institute, Adelaide, Australia

关键词: 1958BC;    SNP-SNP interaction;    SNPs;    RXRG;    VDR;   

Others  :  866580
DOI  :  10.1186/1471-2156-15-37

 received in 2013-09-06, accepted in 2014-03-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Vimaleswaran et al.; licensee BioMed Central Ltd.

【 图 表 】

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