Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK.
BMC Genet. 2014 Mar 19;15:37. doi: 10.1186/1471-2156-15-37.
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.
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).
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.
维生素 D 状态低下已被证实是多种代谢特征的风险因素，如肥胖、糖尿病和心血管疾病。1,25-二羟维生素 D 的生物学作用是通过维生素 D 受体（VDR）介导的，VDR 与视黄酸 X 受体γ（RXRG）形成异二聚体。因此，我们研究了 VDR（22 个标签 SNP）和 RXRG（23 个标签 SNP）基因中的标记多态性与代谢结果（如体重指数、腰围、腰臀比（WHR）、高低密度脂蛋白（LDL）胆固醇、血清甘油三酯、收缩压和舒张压以及糖化血红蛋白）之间的潜在相互作用。我们使用多因子降维（MDR）程序作为一种非参数检验，以研究 1958 年英国出生队列（1958BC，最多 n=5231）中 VDR 和 RXRG 基因多态性之间的潜在相互作用。我们使用了来自芬兰北部出生队列 1966 年（NFBC66，最多 n=5316）和英国双胞胎（最多 n=3943）的数据来复制我们在 1958BC 的初始发现。
在经过 Bonferroni 校正后，联合似然比检验提示在 1958BC 中血清甘油三酯（4 个 SNP-SNP 对）、LDL 胆固醇（2 个 SNP-SNP 对）和 WHR（1 个 SNP-SNP 对）存在相互作用。MDR 置换模型测试分析显示，在 1958BC 中，血清甘油三酯有一个两因素和一个三因素相互作用具有统计学意义。在两个复制队列（NFBC66 和英国双胞胎，总 n=8183）的结果的荟萃分析中，在进行多次检验校正后，没有一个相互作用仍然存在（P（交互作用）>0.17）。
我们的结果没有提供强有力的证据表明 VDR 和 RXRG 基因的等位基因变异在代谢结果之间存在相互作用；然而，需要在大样本中进行进一步的复制研究来证实我们的发现。
