Vitamin D metabolic pathway genes polymorphisms and vitamin D levels in association with neonatal hyperbilirubinemia in China: a single-center retrospective cohort study

Abstract

Background Neonatal hyperbilirubinemia (NH) is a major cause of hospitalization after birth. Previous studies indicated that vitamin D deficiency might play an important role in NH susceptibility, but the results were controversial. Meanwhile, there has been limited description of the association between vitamin D related genes single nucleotide polymorphisms (SNP) and NH susceptibility. We aimed to investigate the vitamin D metabolic pathway genes polymorphisms and vitamin D levels with NH susceptibility. Methods We retrospectively analyzed the clinical data, vitamin D levels and its metabolic pathway gene polymorphisms of 187 NH neonates and 149 controls at Tianjin Children’s Hospital/Tianjin University Children’s Hospital between April 2019 and August 2022. Vitamin D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the genetic polymorphism of NADSYN1/DHCR7, GC, CYP2R1, CYP24A1 and CYP27B1 was detected by high resolution melting (HRM) analysis. Results The frequency of vitamin D deficiency (25(OH)D < 15 ng/mL) was significantly increased in the NH group compared to controls. TT genotype of rs12785878 and GT genotype of rs10877012 were protective factors of vitamin D deficiency and NH, and GT genotype and dominant model carriers of rs12785878 had a higher risk of severe NH than the GG genotype carriers (GT genotype: OR: 2.43; 95% CI: 1.22–4.86; P = 0.012, dominant model: OR: 1.97; 95% CI: 1.04–3.73; P = 0.037). GC gene haplotype was associated with vitamin D deficiency. No significant SNP-SNP and SNP-vitamin D levels interaction combinations were found. Conclusions There were associations among NH, vitamin D deficiency and NADSYN1/DHCR7 and CYP27B1 polymorphisms, TT genotype of rs12785878 and GT genotype of rs10877012 could reduce the risk of vitamin D deficiency and NH. Furthermore, rs12785878 was significantly associated with severe NH.

Genetic Variability in Vitamin D Receptor and Migraine Susceptibility: A Southeastern European Case-Control Study

“…Further to the wide expression of vitamin D receptor (VDR) and vitamin D key metabolic enzymes, including 25-hydroxylase, 1-alpha-hydroxylase (CYP27B1) and CYP24A1 in Central Nervous System (CNS) regions, vitamin D seems to be involved in various physiological brain processes, i.e., brain development, synaptic plasticity, neurotransmission, and cell death prevention [ 25 , 41 , 42 , 43 ]. SNVs in the vitamin D pathway genes, including VDR , CYP2R1 , CYP24A1 and CYP27B1 , were associated with vitamin D serum levels [ 44 , 45 , 46 ]. Although the exact role of vitamin D in migraine remains obscure, vitamin D might be implicated via a variety of proposed mechanisms in the complex pathways involved in the pathophysiology of migraine [ 47 , 48 , 49 , 50 ].…”