Effect of vitamin D receptor polymorphisms on plasma oxidative stress and apoptotic biomarkers among breast cancer survivors supplemented vitamin D3

Abstract

We investigated whether plasma oxidative stress and apoptotic biomarkers were associated with the VDR polymorphisms in breast cancer survivors supplemented with vitamin D3. Two hundred fourteen breast cancer survivors received 4000 IU of vitamin D3 daily for 12 weeks. Linear regression was used to analyze whether the effect of vitamin D3 supplementation on response variables was associated with the selected VDR single nucleotide polymorphisms executing by ‘association’ function in the R package ‘SNPassoc’. Linear regression analyses adjusted for age, BMI and on-study plasma 25(OH)D changes indicated that the aa genotype of the ApaI [codominant model (aa vs. AA): −0.21 (−0.39 to −0.03); recessive model (aa vs. AA and Aa): −0.20 (−0.37 to −0.03)] and bb genotypes of the BsmI [recessive model (bb vs. BB and Bb): −0.20 (−0.39 to −0.01)] on VDR were associated with greater decrease in plasma Bcl2. Our findings indicated that, the Ff genotype of FokI was accompanied by higher increase in plasma MDA levels [codominant model (Ff vs. FF): 0.64 (0.18–1.11); dominant model (ff and Ff vs. FF): 0.52 (0.09–0.05)]. This observed association was not remained statistically significant after correction for multiple testing. Haplotype score analyses revealed statistically significant association between the FokI BsmI ApaI haplotype and circulating MDA changes (P-value for global score = 0.001) after false-discovery rate correction. Our study suggests that genetic variations in the VDR do not powerfully modify the effects of vitamin D3 intake on biomarkers associated with antioxidant activity, oxidative stress and apoptosis in breast cancer survivors.

Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis

“…Of these, 20 articles were excluded because they did not contain the necessary information to carry out the meta-analysis (Supplementary Material Table S2). Therefore, eight studies that fulfilled the inclusion criteria were finally included in the meta-analysis [20,[27][28][29][30][31][32][33]. The response to vitamin D supplementation according to the BsmI polymorphism in the VDR gene was analysed in six studies [20,[27][28][29][30]32].…”

“…Therefore, eight studies that fulfilled the inclusion criteria were finally included in the meta-analysis [20,[27][28][29][30][31][32][33]. The response to vitamin D supplementation according to the BsmI polymorphism in the VDR gene was analysed in six studies [20,[27][28][29][30]32]. Five studies analysed the vitamin D response according to the genotypic distribution of the TaqI genetic variant [27][28][29][30]32].…”

“…The response to vitamin D supplementation according to the BsmI polymorphism in the VDR gene was analysed in six studies [20,[27][28][29][30]32]. Five studies analysed the vitamin D response according to the genotypic distribution of the TaqI genetic variant [27][28][29][30]32]. The influence of the ApaI polymorphism was studied in four articles [27,29,30,32].…”

“…Five studies analysed the vitamin D response according to the genotypic distribution of the TaqI genetic variant [27][28][29][30]32]. The influence of the ApaI polymorphism was studied in four articles [27,29,30,32]. Finally, the influence of the FokI polymorphism in the response to vitamin D supplementation was analysed in five studies [27,[29][30][31]33].…”

Effect of Vitamin D Deficiency and Supplementation in Lactation and Early Life on Allergic Airway Inflammation and the Expression of Autophagy-Related Genes in an Ovalbumin Mouse Model

“…Although 1,25(OH) 2 D 3 is most commonly thought to regulate calcium homeostasis that affects bone metabolism, the wide distribution of vitamin D receptor (VDR) suggests that vitamin D may have much broader functions, including playing roles in apoptosis, inflammation, immunomodulation, and autophagy. [9][10][11][12] The relationship between vitamin D and autophagy in innate immunity, inflammatory bowel diseases, infection, and cancer [13][14][15][16] has been the subject of recent investigation. Studies have shown that vitamin D suppressed experimental autoimmune encephalomyelitis-induced LC3 in the brain 13 or angiotensin II-induced LC3 in the kidney, 14 while it increased LC3 II and Beclin-1 in enteroids 15 and human peritoneal mesothelial cells.…”