High-Dose Vitamin D During Pregnancy and Pathway Gene Polymorphisms in Prevention of Offspring Persistent Wheeze

Nicklas Brustad, Jens H Greve, Hooman Mirzakhani, Casper-Emil T Pedersen, Anders U Eliasen, Jakob Stokholm, Jessica Lasky-Su, Klaus Bønnelykke, Augusto A Litonjua, Scott T Weiss, Hans Bisgaard, Bo L Chawes

7 Citationer (Scopus)

Abstract

BACKGROUND: Randomized controlled trials (RCTs) suggest a protective effect of high-dose vitamin D supplementation in pregnancy on offspring risk of persistent wheeze, but only in some individuals, which might be explained by variations in vitamin D pathway genes. This study aimed to investigate the effect of vitamin D supplementation by maternal and offspring vitamin D receptor (VDR) genotype and GC genotype, encoding vitamin D binding protein (VDBP), in two RCTs.

METHODS: In the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC 2010 ) RCT, we analyzed the effect of high-dose vitamin D during pregnancy on the risk of persistent wheeze age 0-3 years by variants in single nucleotide polymorphisms (SNPs) in VDR (rs1544410, rs2228570, rs7975128, rs7975232) and GC (rs4588, rs7041). Replication was sought in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

RESULTS: In COPSAC 2010 , VDR SNP rs1544410 influenced the effect of high-dose vitamin D: maternal P interaction = .049 and child P interaction = .001, with the largest effect in offspring from mothers with TT genotype: hazard ratio (95% CI), 0.26 (0.10-0.68), P = .006, and no effect among CT or CC genotypes: 0.85 (0.48-1.51), P = .58 and 0.94 (0.47-1.89), P = .87, respectively. However, these findings were not replicated in VDAART. There was no significant effect modification from maternal or offspring GC genotype in either COPSAC 2010 or VDAART: all P interaction ≥ .17.

CONCLUSIONS: We found that the effect of high-dose vitamin D supplementation during pregnancy on offspring risk of persistent wheeze was significantly influenced by VDR genotype in the COPSAC 2010 RCT, but not VDAART, which may be due to population differences.

OriginalsprogEngelsk
TidsskriftPediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Vol/bind32
Udgave nummer4
Sider (fra-til)679-689
Antal sider11
ISSN0905-6157
DOI
StatusUdgivet - maj 2021

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