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01-10-2015 | Article

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

Authors: Maija E. Miettinen, Melissa C. Smart, Leena Kinnunen, Christopher Mathews, Valma Harjutsalo, Heljä-Marja Surcel, Christel Lamberg-Allardt, Jaakko Tuomilehto, Graham A. Hitman

Published in: Diabetologia | Issue 10/2015

Abstract

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.

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Title: Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring
Authors: Maija E. Miettinen
Melissa C. Smart
Leena Kinnunen
Christopher Mathews
Valma Harjutsalo
Heljä-Marja Surcel
Christel Lamberg-Allardt
Jaakko Tuomilehto
Graham A. Hitman
Publication date: 01-10-2015
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 10/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-015-3675-8

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Abstract

Aims/hypothesis

Methods

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