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- Title
Leptin and IGF-1 in Infancy Are Associated With Variants in DHCR7 and CYP2R1 That Relate With Type 1 Diabetes and 25OHD.
- Authors
Eleftheriou, Antigoni; Ong, Ken K.; Hughes, Ieuan A.; Petry, Clive J.
- 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 (ß = -.11, P = .02) and rs12794714 (ß = -.09, P = .04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (ß = .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 (ß = .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.
- Subjects
LEPTIN; SOMATOMEDIN C; TYPE 1 diabetes
- Publication
Journal of Clinical Endocrinology & Metabolism, 2023, Vol 108, Issue 11, pe1394
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgad263