Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring

Diabetologia. 2015 Oct;58(10):2278-83. doi: 10.1007/s00125-015-3675-8. Epub 2015 Jun 26.


Aims/hypothesis: We investigated whether single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentration in the metabolic pathway of vitamin D show different genotype distributions between Finnish families with an offspring with type 1 diabetes (cases) and families with a healthy offspring (controls).

Methods: A total of 31 SNPs in eight genes were studied in case and control mothers and family members (offspring with type 1 diabetes and healthy siblings, healthy control children and fathers) (n = 2,854). The 25-hydroxyvitamin D concentration was studied in 474 case and 348 matched control mothers during pregnancy.

Results: The genotype distributions of 13 SNPs (in the following genes: 7-dehydrocholesterol reductase NADSYN1/DHCR7, vitamin D receptor VDR, group-specific component GC and CYP27A1) that showed a nominal association with 25-hydroxyvitamin D concentration (p < 0.05) were compared between case and control families. SNPs in VDR had different genotype distributions between the case and control mothers (rs1544410, p = 0.007; rs731236, p = 0.003; rs4516035, p = 0.015), two SNPs (rs1544410 and rs731236) remaining significant after correction for multiple testing using a false discovery rate. The mean 25-hydroxyvitamin D concentrations during pregnancy did not differ between the case and control mothers.

Conclusions/interpretation: Our preliminary results suggest that the maternal genotypes of SNPs in VDR may influence the in utero environment and thus contribute to the early programming of type 1 diabetes in the fetus. It is possible that the effects are only relevant in the presence of vitamin D insufficiency.

Keywords: 25-Hydroxyvitamin D; In utero; Maternal genotype; Pregnancy; Type 1 diabetes; VDR; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Receptors, Calcitriol / genetics*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Receptors, Calcitriol
  • Vitamin D
  • 25-hydroxyvitamin D