Lyndsey E Shorey-Kendrick, Cindy T McEvoy, Kristin Milner, Julia Harris, Julie Brownsberger, Robert S Tepper, Byung Park, Lina Gao, Annette Vu, Cynthia D Morris, Emma E Thompson, Carole Ober, Eliot R Spindel
{"title":"孕妇吸烟者补充维生素C可改变5岁儿童口腔DNA中与哮喘和过敏相关的CpGs。","authors":"Lyndsey E Shorey-Kendrick, Cindy T McEvoy, Kristin Milner, Julia Harris, Julie Brownsberger, Robert S Tepper, Byung Park, Lina Gao, Annette Vu, Cynthia D Morris, Emma E Thompson, Carole Ober, Eliot R Spindel","doi":"10.1186/s13148-025-01965-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We previously reported improved respiratory outcomes in babies born to pregnant smokers supplemented with vitamin C (500 mg/day) versus placebo in a randomized clinical trial. Improved respiratory outcomes persisted to 5 years of age and were associated with buccal DNA methylation (DNAm) measured using the InfiniumMethylationEPIC array. The objective of this study was to examine associations of vitamin C treatment and lung function with buccal DNAm using a custom-content Asthma&Allergy array enriched for asthma and allergy loci likely to have a functional impact on gene expression.</p><p><strong>Results: </strong>We profiled DNAm at 36,999 CpGs in loci previously associated with asthma or allergic diseases using custom-content Asthma&Allergy arrays in 137 subjects (65 placebo; 72 vitamin C) with pulmonary function testing (PFT) at the 5-year visit in the \"Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function\" (VCSIP) double-blind, placebo-controlled randomized clinical trial. We examined the association of buccal DNAm with (1) vitamin C treatment vs placebo, (2) forced expiratory flow between 25 and 75% of expired volume (FEF<sub>25-75</sub>) and (3) wheeze at 4-6 years of age. We identified 9 genome-wide differentially methylated CpGs (DMCs; FDR < 0.05) and 2 differentially methylated regions (DMRs) between vitamin C and placebo subjects and one CpG associated with FEF<sub>25-75</sub> at FDR significance. DNAm at 5 CpGs mediated a significant proportion of the vitamin C treatment effect on lung function, including 2 CpGs annotated to the SLC25A37 gene involved in mitochondrial iron transport.</p><p><strong>Conclusions: </strong>Our study revealed association of in utero vitamin C supplementation and childhood lung function with DNAm at novel loci, providing additional insight toward potential mechanisms for the persistent effects of vitamin C supplementation to pregnant smokers.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT01723696 (Registered on November 6, 2011) and NCT03203603 (Registered on March 28, 2017).</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"155"},"PeriodicalIF":4.4000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495669/pdf/","citationCount":"0","resultStr":"{\"title\":\"Vitamin C supplementation to pregnant smokers alters asthma- and allergy-associated CpGs in child buccal DNA at 5 years of age.\",\"authors\":\"Lyndsey E Shorey-Kendrick, Cindy T McEvoy, Kristin Milner, Julia Harris, Julie Brownsberger, Robert S Tepper, Byung Park, Lina Gao, Annette Vu, Cynthia D Morris, Emma E Thompson, Carole Ober, Eliot R Spindel\",\"doi\":\"10.1186/s13148-025-01965-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We previously reported improved respiratory outcomes in babies born to pregnant smokers supplemented with vitamin C (500 mg/day) versus placebo in a randomized clinical trial. Improved respiratory outcomes persisted to 5 years of age and were associated with buccal DNA methylation (DNAm) measured using the InfiniumMethylationEPIC array. The objective of this study was to examine associations of vitamin C treatment and lung function with buccal DNAm using a custom-content Asthma&Allergy array enriched for asthma and allergy loci likely to have a functional impact on gene expression.</p><p><strong>Results: </strong>We profiled DNAm at 36,999 CpGs in loci previously associated with asthma or allergic diseases using custom-content Asthma&Allergy arrays in 137 subjects (65 placebo; 72 vitamin C) with pulmonary function testing (PFT) at the 5-year visit in the \\\"Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function\\\" (VCSIP) double-blind, placebo-controlled randomized clinical trial. We examined the association of buccal DNAm with (1) vitamin C treatment vs placebo, (2) forced expiratory flow between 25 and 75% of expired volume (FEF<sub>25-75</sub>) and (3) wheeze at 4-6 years of age. We identified 9 genome-wide differentially methylated CpGs (DMCs; FDR < 0.05) and 2 differentially methylated regions (DMRs) between vitamin C and placebo subjects and one CpG associated with FEF<sub>25-75</sub> at FDR significance. DNAm at 5 CpGs mediated a significant proportion of the vitamin C treatment effect on lung function, including 2 CpGs annotated to the SLC25A37 gene involved in mitochondrial iron transport.</p><p><strong>Conclusions: </strong>Our study revealed association of in utero vitamin C supplementation and childhood lung function with DNAm at novel loci, providing additional insight toward potential mechanisms for the persistent effects of vitamin C supplementation to pregnant smokers.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT01723696 (Registered on November 6, 2011) and NCT03203603 (Registered on March 28, 2017).</p>\",\"PeriodicalId\":10366,\"journal\":{\"name\":\"Clinical Epigenetics\",\"volume\":\"17 1\",\"pages\":\"155\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495669/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Epigenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13148-025-01965-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-025-01965-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Vitamin C supplementation to pregnant smokers alters asthma- and allergy-associated CpGs in child buccal DNA at 5 years of age.
Background: We previously reported improved respiratory outcomes in babies born to pregnant smokers supplemented with vitamin C (500 mg/day) versus placebo in a randomized clinical trial. Improved respiratory outcomes persisted to 5 years of age and were associated with buccal DNA methylation (DNAm) measured using the InfiniumMethylationEPIC array. The objective of this study was to examine associations of vitamin C treatment and lung function with buccal DNAm using a custom-content Asthma&Allergy array enriched for asthma and allergy loci likely to have a functional impact on gene expression.
Results: We profiled DNAm at 36,999 CpGs in loci previously associated with asthma or allergic diseases using custom-content Asthma&Allergy arrays in 137 subjects (65 placebo; 72 vitamin C) with pulmonary function testing (PFT) at the 5-year visit in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) double-blind, placebo-controlled randomized clinical trial. We examined the association of buccal DNAm with (1) vitamin C treatment vs placebo, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25-75) and (3) wheeze at 4-6 years of age. We identified 9 genome-wide differentially methylated CpGs (DMCs; FDR < 0.05) and 2 differentially methylated regions (DMRs) between vitamin C and placebo subjects and one CpG associated with FEF25-75 at FDR significance. DNAm at 5 CpGs mediated a significant proportion of the vitamin C treatment effect on lung function, including 2 CpGs annotated to the SLC25A37 gene involved in mitochondrial iron transport.
Conclusions: Our study revealed association of in utero vitamin C supplementation and childhood lung function with DNAm at novel loci, providing additional insight toward potential mechanisms for the persistent effects of vitamin C supplementation to pregnant smokers.
Clinical trial registration: ClinicalTrials.gov, NCT01723696 (Registered on November 6, 2011) and NCT03203603 (Registered on March 28, 2017).
期刊介绍：
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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