OBJECTIVE We investigated whether vitamin D receptor (VDR) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. METHODS One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. RESULTS One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI, the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [- 17.9(- 33.6, - 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI, ApaI, TaqI and FokI, BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. CONCLUSIONS Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. TRIAL REGISTRATION This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU).

中文翻译：

---

维生素 D 受体基因多态性影响补充维生素 D3 的乳腺癌幸存者内脏脂肪、腰围和血脂的变化。

目的 我们研究维生素 D 受体 (VDR) 多态性是否与补充维生素 D3 的乳腺癌幸存者的循环代谢生物标志物和人体测量变化相关。方法 入住 Shohaday-e-Tajrish 医院的 168 名乳腺癌幸存者每天服用 4000 IU 维生素 D3 补充剂，持续 12 周。在干预前后进行人体测量以及饮食、体力活动和血浆代谢生物标志物评估。VDR 多态性被认为是主要暴露因素。使用多变量多元线性回归分析来确定 VDR 单核苷酸多态性 (SNP) 与补充维生素 D3 后代谢和人体测量指标变化之间的关联。结果 125 名 (85%) 女性基线时血浆 25-羟基维生素 D (25(OH)D) 水平不足。与 ApaI 的 AA 基因型相比，在调整潜在混杂因素后，aa 类别显示出肌肉质量 [71.3(10.7131.9)] 的更大增加和 LDL-C [- 17.9(- 33.6, - 2.3)] 水平的更大降低。此外，与 BB 相比，BsmI VDR 杂合基因型 (Bb) 与补充维生素 D3 后 WC 的较高增加相关 [2.7(0.1,5.3)]。单倍型评分分析表明，从 BsmI、ApaI、TaqI 和 FokI、BsmI 和 Cdx2 VDR 多态性推断的单倍型与研究中内脏脂肪变化之间存在显着关联。结论 这项研究的结果表明，VDR 基因的遗传变异与乳腺癌幸存者心脏代谢参数的变化相关，补充维生素 D3 后，结果可以为更好地了解哪些个体亚群从正常化中受益最多提供新的见解维生素 D 状态。试验注册 该试验已在伊朗临床试验注册处（IRCT）注册，识别码：IRCT2017091736244N1，注册日期：2017-11-10，http://www.irct.ir/Trial/27153，并获得批准国家营养与食品技术研究所 (NNFTRI)、沙希德·贝赫什提医科大学 (SBMU) 的伦理委员会。