孕期血清25-羟维生素D浓度与儿童1型糖尿病的遗传决定因素。
Genetic determinants of serum 25-hydroxyvitamin D concentration during pregnancy and type 1 diabetes in the child.
作者信息
Miettinen Maija E, Smart Melissa C, Kinnunen Leena, Harjutsalo Valma, Reinert-Hartwall Linnea, Ylivinkka Irene, Surcel Heljä-Marja, Lamberg-Allardt Christel, Hitman Graham A, Tuomilehto Jaakko
机构信息
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
出版信息
PLoS One. 2017 Oct 4;12(10):e0184942. doi: 10.1371/journal.pone.0184942. eCollection 2017.
OBJECTIVE
The in utero environment plays an important role in shaping development and later life health of the fetus. It has been shown that maternal genetic factors in the metabolic pathway of vitamin D associate with type 1 diabetes in the child. In this study we analyzed the genetic determinants of serum 25-hydroxyvitamin D (25OHD) concentration during pregnancy in mothers whose children later developed type 1 diabetes and in control mothers.
STUDY DESIGN
474 mothers of type 1 diabetic children and 348 mothers of non-diabetic children were included in the study. We previously selected 7 single nucleotide polymorphisms (SNPs) in four genes in the metabolic pathway of vitamin D vitamin based on our previously published data demonstrating an association between genotype and serum 25OHD concentration. In this re-analysis, possible differences in strength in the association between the SNPs and serum 25OHD concentration in mothers of type 1 diabetic and non-diabetic children were investigated. Serum 25OHD concentrations were previously shown to be similar between the mothers of type 1 diabetic and non-diabetic children and vitamin D deficiency prevalent in both groups.
RESULTS
Associations between serum 25OHD concentration and 2 SNPs, one in the vitamin D receptor (VDR) gene (rs4516035) and one in the group-specific component (GC) gene (rs12512631), were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not (pinteraction = 0.03, 0.02, respectively).
CONCLUSIONS
We show for the first time that there are differences in the strength of genetic determinants of serum 25OHD concentration during pregnancy between the mothers of type 1 diabetic and non-diabetic children. Our results emphasize that the in utero environment including maternal vitamin D metabolism should be important lines of investigation when searching for factors that lead to early programming of type 1 diabetes.
目的
子宫内环境在塑造胎儿发育及日后健康方面起着重要作用。研究表明，维生素D代谢途径中的母体遗传因素与儿童1型糖尿病相关。在本研究中，我们分析了孩子后来患1型糖尿病的母亲以及对照母亲孕期血清25-羟维生素D（25OHD）浓度的遗传决定因素。
研究设计
本研究纳入了474名1型糖尿病患儿的母亲和348名非糖尿病患儿的母亲。基于我们之前发表的数据显示基因型与血清25OHD浓度之间存在关联，我们先前在维生素D代谢途径的四个基因中选择了7个单核苷酸多态性（SNP）。在本次重新分析中，研究了1型糖尿病患儿母亲和非糖尿病患儿母亲中SNP与血清25OHD浓度之间关联强度的可能差异。先前研究表明，1型糖尿病患儿母亲和非糖尿病患儿母亲的血清25OHD浓度相似，且两组中维生素D缺乏症都很普遍。
结果
血清25OHD浓度与两个SNP之间的关联，一个位于维生素D受体（VDR）基因（rs4516035），另一个位于组特异性成分（GC）基因（rs12512631），在孩子后来患1型糖尿病的母亲孕期比孩子未患1型糖尿病的母亲更强（交互作用P值分别为0.03和0.02）。
结论
我们首次表明，1型糖尿病患儿母亲和非糖尿病患儿母亲在孕期血清25OHD浓度遗传决定因素的强度存在差异。我们的结果强调，在寻找导致1型糖尿病早期编程的因素时，包括母体维生素D代谢在内的子宫内环境应是重要的研究方向。
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