Leptin and IGF-1 in Infancy Are Associated With Variants in DHCR7 and CYP2R1 That Relate With Type 1 Diabetes and 25OHD

Author:

Eleftheriou Antigoni1ORCID,Ong Ken K123ORCID,Hughes Ieuan A1ORCID,Petry Clive J1ORCID

Affiliation:

1. Department of Paediatrics, University of Cambridge , Cambridge CB2 0QQ , UK

2. MRC Epidemiology Unit, University of Cambridge , Cambridge CB2 0QQ , UK

3. Institute of Metabolic Science, University of Cambridge , Cambridge CB2 0QQ , UK

Abstract

Abstract Context Vitamin D has been variably implicated in risk of developing type 1 diabetes based on cohorts of at-risk individuals. Emergent type 1 diabetes in childhood is putatively preceded by altered growth. Objective We explored whether polymorphisms in vitamin D metabolism genes modify risk of type 1 diabetes via effects on growth in a prospective, population-based cohort of infants. Methods The Cambridge Baby Growth Study enrolled newborns from Cambridgeshire, UK, for follow-up in infancy. In 612 infants, we genotyped single nucleotide polymorphisms in vitamin D metabolism genes that relate with type 1 diabetes: rs10741657 and rs12794714 in CYP2R1, rs12785878 in DHCR7, and rs10877012 in CYP27B1. Multivariate linear regression analyses tested associations between genotypes and anthropometric indices (weight, length, and skinfold thickness) or growth-related hormones (C-peptide, IGF-1, and leptin) in infancy. Results Birth weight showed borderline associations with the diabetes risk–increasing alleles in CYP2R1, rs10741657 (β = −.11, P = .02) and rs12794714 (β = −.09, P = .04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (β = .30, P = .01). At age 3 months, the risk-increasing allele rs12785878 in DHCR7, known to negatively associate with 25-hydroxyvitamin D levels, showed a positive association with leptin levels (β = .23, P = .009), which was pronounced in girls (P = .004) vs boys (P = .7). Conclusion The vitamin D metabolism genes DHCR7 and CYP2R1 might influence infancy leptin and IGF-1 levels respectively. These findings open the possibility for a developmental role of vitamin D that is mediated by growth-related hormones with implications for the onset of type 1 diabetes autoimmunity.

Funder

Medical Research Council

Raymond & Beverly Sackler Foundation

European Union Framework 5

Mothercare Charitable Foundation

Newlife Foundation for Disabled Children

World Cancer Research Fund International

National Institute for Health Research Cambridge Biomedical Research Centre

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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