Leptin and IGF-1 in infancy are associated with variants in DHCR7 and CYP2R1 that relate with type 1 diabetes and 25OHD.
The Journal of clinical endocrinology and metabolism 2023
DOI : 10.1210/clinem/dgad263
PubMed ID : 37170809
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.
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.
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.
Birth weight showed borderline associations with the diabetes risk-increasing alleles in CYP2R1, rs10741657 (β=-0.11, P=0.02) and rs12794714 (β=-0.09, P=0.04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (β=0.30, P=0.01). At age 3 months, the risk-increasing allele rs12785878 in DHCR7, known to negatively associate with 25OHD levels, showed a positive association with leptin levels (β=0.23, P=0.009), which was pronounced in girls (P=0.004) vs. boys (P=0.7).
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.