High-dose vitamin D during pregnancy and pathway gene polymorphisms in prevention of offspring persistent wheeze
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High-dose vitamin D during pregnancy and pathway gene polymorphisms in prevention of offspring persistent wheeze. / Brustad, Nicklas; Greve, Jens H; Mirzakhani, Hooman; Pedersen, Casper-Emil T.; Eliasen, Anders U; Stokholm, Jakob; Lasky-Su, Jessica; Bønnelykke, Klaus; Litonjua, Augusto A; Weiss, Scott T; Bisgaard, Hans; Chawes, Bo L.
I: Pediatric Allergy and Immunology, Bind 32, Nr. 4, 2021, s. 679-689.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - High-dose vitamin D during pregnancy and pathway gene polymorphisms in prevention of offspring persistent wheeze
AU - Brustad, Nicklas
AU - Greve, Jens H
AU - Mirzakhani, Hooman
AU - Pedersen, Casper-Emil T.
AU - Eliasen, Anders U
AU - Stokholm, Jakob
AU - Lasky-Su, Jessica
AU - Bønnelykke, Klaus
AU - Litonjua, Augusto A
AU - Weiss, Scott T
AU - Bisgaard, Hans
AU - Chawes, Bo L
N1 - © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2021
Y1 - 2021
N2 - 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 (COPSAC2010 ) 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 COPSAC2010 , VDR SNP rs1544410 influenced the effect of high-dose vitamin D: maternal Pinteraction = .049 and child Pinteraction = .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 COPSAC2010 or VDAART: all Pinteraction ≥ .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 COPSAC2010 RCT, but not VDAART, which may be due to population differences.
AB - 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 (COPSAC2010 ) 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 COPSAC2010 , VDR SNP rs1544410 influenced the effect of high-dose vitamin D: maternal Pinteraction = .049 and child Pinteraction = .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 COPSAC2010 or VDAART: all Pinteraction ≥ .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 COPSAC2010 RCT, but not VDAART, which may be due to population differences.
U2 - 10.1111/pai.13453
DO - 10.1111/pai.13453
M3 - Journal article
C2 - 33453076
VL - 32
SP - 679
EP - 689
JO - Pediatric Allergy and Immunology, Supplement
JF - Pediatric Allergy and Immunology, Supplement
SN - 0906-5784
IS - 4
ER -
ID: 259830108