{"doi":"10.1183/13993003.02012-2020","title":"Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze","abstract":"Background Prenatal vitamin D 3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D 3 supplementation against offspring asthma/recurrent wheeze. Methods We determined the rs12936231 genotype of mother–child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010 , n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0–3 years between groups who received high-dose prenatal vitamin D 3 supplementation versus placebo. Results Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D 3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37–0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35–0.92; p=0.021 for COPSAC 2010 ), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61–1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54–2.28; p=0.785 for COPSAC 2010 ). Conclusion Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D 3 supplementation against offspring asthma/recurrent wheeze.","journal":"European Respiratory Journal","year":2021,"id":186254,"datarank":0.7342615854368082,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.2575535108846163,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.2575535108846163,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00920621","NCT00856947"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":285327,"name":"Rachel S. Kelly","orcid":"0000-0003-3023-1822","position":1,"is_corresponding":false},{"id":657145,"name":"Nicklas Brustad","orcid":"0000-0001-6383-8845","position":2,"is_corresponding":false},{"id":516029,"name":"Mengna Huang","orcid":"0000-0002-4626-4816","position":3,"is_corresponding":false},{"id":218548,"name":"Priyadarshini Kachroo","orcid":"0000-0002-5807-1333","position":4,"is_corresponding":false},{"id":241480,"name":"Bo Chawes","orcid":"0000-0001-6846-6243","position":5,"is_corresponding":false},{"id":241503,"name":"Jakob Stokholm","orcid":"0000-0003-4989-9769","position":6,"is_corresponding":false},{"id":241476,"name":"Klaus Bønnelykke","orcid":"0000-0003-2003-1018","position":7,"is_corresponding":false},{"id":657143,"name":"Casper‐Emil Tingskov Pedersen","orcid":"0000-0003-2540-5373","position":8,"is_corresponding":false},{"id":255256,"name":"Hans Bisgaard","orcid":"0000-0003-4131-7592","position":9,"is_corresponding":false},{"id":252193,"name":"Augusto A. Litonjua","orcid":"0000-0003-0422-5875","position":10,"is_corresponding":false},{"id":218538,"name":"Jessica Lasky‐Su","orcid":"0000-0001-6236-4705","position":11,"is_corresponding":false},{"id":25033,"name":"Scott T. Weiss","orcid":"0000-0001-7196-303X","position":12,"is_corresponding":false},{"id":657146,"name":"Hanna Knihtilä","orcid":"0000-0001-7339-1880","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"33653805","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}