Mehramiz Mehrane, Khayyatzadeh Sayyed Saeid, Esmaily Habibollah, Ghasemi Faezeh, Sadeghi-Ardekani Kiana, Tayefi Maryam, Mirmousavi Seyed Jamal, Hanachi Parichehr, Bahrami-Taghanaki H, Eslami Saeed, Vatanparast Hasan, Ferns Gordon A, Ghayour-Mobarhan Majid, Avan Amir
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Clin Nutr ESPEN. 2019 Feb;29:59-64. doi: 10.1016/j.clnesp.2018.12.005. Epub 2018 Dec 28.
Vitamin D deficiency is a global problem that may be improved by vitamin D supplementation; however, the individual's response to the intervention varies. We aimed to investigate possible genetic factors that may modify the impact of environmental exposure on vitamin D status. The candidate gene variant we investigated was the Gc gene-rs4588 polymorphism at the vitamin D receptor (DBP) locus.
A total of 619 healthy adolescent Iranian girls received 50000 IU of vitamin D weekly for 9 weeks. Serum 25(OH) D concentrations, metabolic profiles and dietary intake were measured at baseline and after 9 weeks of supplementation. The genotypes of the DBP variant (rs4588) were analyzed using the TaqMan genotyping assay.
Our results revealed that the rs4588 polymorphism might be associated with serum 25-hydroxy vitamin D both at baseline (p value = 0.03) and after intervention (p value = 0.008). It seemed that the outcome of the intervention was gene-related so that the subjects with common AA genotype were a better responder to vitamin D supplementation (Changes (%) 469.5 (427.1) in AA carriers vs. 335.8 (530) in GG holders), and carriers of the less common GG genotype experienced a rise in fasting blood glucose after 9 weeks (Changes (%) 0 (1.5)). Our findings also showed that the statistical interaction between this variant and supplementation was statistically significant (intervention effect p-value<0.001 and p-value SNP effect = 0.03). The regression model also revealed that after adjusted for potential confounders, likelihood of affecting serum 25(OH)D in individuals who were homozygous for the uncommon allele G was less than those homozygous for the more common AA genotype (OR = 4.407 (1.82-8.89); p = 0.001).
Serum vitamin 25(OH) D following vitamin 25(OH) D supplementation appears to be modified by genetic background. The Gc genetic variant, rs4588 encoding the vitamin D receptor seems to influence the response to vitamin D supplementation.
维生素D缺乏是一个全球性问题，补充维生素D可能会改善这一状况；然而，个体对干预的反应各不相同。我们旨在研究可能改变环境暴露对维生素D状态影响的遗传因素。我们研究的候选基因变异是维生素D受体（DBP）位点的Gc基因-rs4588多态性。
总共619名健康的伊朗青春期女孩每周接受50000国际单位的维生素D，持续9周。在基线期和补充9周后测量血清25(OH)D浓度、代谢谱和饮食摄入量。使用TaqMan基因分型检测分析DBP变异（rs4588）的基因型。
我们的结果显示，rs4588多态性在基线期（p值 = 0.03）和干预后（p值 = 0.008）可能都与血清25-羟维生素D有关。干预结果似乎与基因有关，因此具有常见AA基因型的受试者对维生素D补充的反应更好（AA携带者的变化（%）为469.5（427.1），而GG基因型者为335.8（530）），而较不常见的GG基因型携带者在9周后空腹血糖升高（变化（%）为0（1.5））。我们的研究结果还表明，该变异与补充之间的统计相互作用具有统计学意义（干预效应p值<0.001，SNP效应p值 = 0.03）。回归模型还显示，在调整潜在混杂因素后，罕见等位基因G纯合个体影响血清25(OH)D的可能性低于常见AA基因型纯合个体（OR = 4.407（1.82 - 8.89）；p = 0.001）。
补充维生素25(OH)D后血清维生素25(OH)D似乎受遗传背景影响。编码维生素D受体的Gc基因变异rs4588似乎会影响对维生素D补充的反应。
