title: Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: National Institute for Health and Welfare, Chronic Disease Prevention Unit, PO Box 30, 00271, Helsinki, Finland. maija.miettinen@thl.fi.
authors.forename: Maija E
authors.initials: ME
authors.lastname: Miettinen
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Smart
authors.affiliation: National Institute for Health and Welfare, Chronic Disease Prevention Unit, PO Box 30, 00271, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Kinnunen
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Mathews
authors.affiliation: National Institute for Health and Welfare, Chronic Disease Prevention Unit, PO Box 30, 00271, Helsinki, Finland.|Folkhälsan Institute of Genetics, Folkhälsan Research Center, University of Helsinki, Helsinki, Finland.|Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Valma
authors.initials: V
authors.lastname: Harjutsalo
authors.affiliation: Impact Assessment Unit, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Heljä-Marja
authors.initials: HM
authors.lastname: Surcel
authors.affiliation: Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Christel
authors.initials: C
authors.lastname: Lamberg-Allardt
authors.affiliation: National Institute for Health and Welfare, Chronic Disease Prevention Unit, PO Box 30, 00271, Helsinki, Finland.|Center for Vascular Prevention, Danube-University Krems, Krems, Austria.|South Ostrobothnia Central Hospital, Seinäjoki, Finland.|Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-Hydroxyvitamin D; In utero; Maternal genotype; Pregnancy; Type 1 diabetes; VDR; Vitamin D