Genetic determinants of serum 25-hydroxyvitamin D concentration during pregnancy and type 1 diabetes in the child.

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.Funded by The Finnish Academy (Grant No. 127219) (http://www.aka.fi/en/); The European Foundation for the Study of Diabetes (http://www.europeandiabetesfoundation.org/); Novo Nordisk Foundation (http://novonordiskfonden.dk/en); Diabetes Research Foundation (https://www.diabetestutkimus.fi/); South Ostrobothnia Central Hospital (EVO1107) (http://www.epshp.fi/en); Biomedicum Helsinki Foundation (http://www.biomedicum.fi/index.php?page=112&lang=2); Jalmari and Rauha Ahokas Foundation (http://www.ahokkaansaatio.org/); Yrjö Jahnsson Foundation (http://www.yjs.fi/en/); Suoma Loimaranta-Airila Fund (http://www.european-funding-guide.eu/scholarship/14903-scholarship); Onni and Hilja Tuovinen Foundation (http://www.tuovisensaatio.fi/); Juho Vainio Foundation (http://juhovainionsaatio.fi/en/juho-vainio-foundation/); Orion Research Foundation (http://www.orion.fi/tutkimus/orionin-tutkimussaatio/); Kyllikki and Uolevi Lehikoinen Foundation (http://www.aurora-tietokanta.fi/grant/details/id/4096/refc/foundation/refa/details). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript