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Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight

Preterm delivery (PTD) is an adverse birth outcome associated with increased infant mortality and negative lifelong health consequences. PTD may be the result of interactions between genetics and maternal/fetal environmental factors including smoking exposure (SMK). A common deletion in the GSTT1 ge...

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Autores principales: Zheng, Xiaojing, Feingold, Eleanor, Ryckman, Kelli K., Shaffer, John R., Boyd, Heather A., Feenstra, Bjarke, Melbye, Mads, Marazita, Mary L., Murray, Jeffrey C., Cuenco, Karen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809558/
https://www.ncbi.nlm.nih.gov/pubmed/24194744
http://dx.doi.org/10.3389/fgene.2013.00196
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author Zheng, Xiaojing
Feingold, Eleanor
Ryckman, Kelli K.
Shaffer, John R.
Boyd, Heather A.
Feenstra, Bjarke
Melbye, Mads
Marazita, Mary L.
Murray, Jeffrey C.
Cuenco, Karen T.
author_facet Zheng, Xiaojing
Feingold, Eleanor
Ryckman, Kelli K.
Shaffer, John R.
Boyd, Heather A.
Feenstra, Bjarke
Melbye, Mads
Marazita, Mary L.
Murray, Jeffrey C.
Cuenco, Karen T.
author_sort Zheng, Xiaojing
collection PubMed
description Preterm delivery (PTD) is an adverse birth outcome associated with increased infant mortality and negative lifelong health consequences. PTD may be the result of interactions between genetics and maternal/fetal environmental factors including smoking exposure (SMK). A common deletion in the GSTT1 gene was previously reported to affect birth outcomes in smokers. In this study, we dissect the associations among SMK, birth outcomes, and copy number variations (CNVs) in the GSTT1/GSTT2 region. A preterm birth case-control dataset of 1937 mothers was part of the GENEVA preterm birth study, which included genome-wide genotyping used to identify CNVs. We examined the association of SMK with birth outcomes, detected CNVs within the GSTT1/GSTT2 region using PennCNV, and examined associations of the identified CNVs with preterm birth and with birth weight (BW) in full term birth controls, including interactions with SMK. Finally, we tested the association of CNVs in GSTT1/GSTT2 with SMK. We confirmed the association of smoking with low BW and PTD. We identified 2 CNVs in GSTT2 (GSTT2(a) and GSTT2(b)), 1 CNV in GSTTP1 and 2 CNVs in GSTT1 (GSTT1(a) and GSTT1(b)). The GSTT2(a) deletion was associated with reduced BW (−284 g, p = 2.50E-7) in smokers, and was more common in smokers [odds ratio(OR) = 1.30, p = 0.04]. We found that the size of the reported common deletion CNV in GSTT1 was larger than previously shown. The GSTTP1 and GSTT1(b) null genotypes were in high linkage disequilibrium (LD) (D′ = 0.89) and less common in smokers (OR = 0.68, p = 0.019 and OR = 0.73, p = 0.055, respectively). These two deletions were in partial LD with GSTT2(a) and GSTT2(b) duplications. All 5 CNVs seem to be associated with increased risk of preterm birth before 35 completed weeks. CNVs in the GSTTT1/GSTT2 region appear associated with low BW and PTD outcomes, but LD complicated these CNVs in GSTT1/GSTT2. In genetic association studies of BW, multiple CNVs in this region need to be investigated instead of a single polymorphism.
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spelling pubmed-38095582013-11-05 Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight Zheng, Xiaojing Feingold, Eleanor Ryckman, Kelli K. Shaffer, John R. Boyd, Heather A. Feenstra, Bjarke Melbye, Mads Marazita, Mary L. Murray, Jeffrey C. Cuenco, Karen T. Front Genet Genetics Preterm delivery (PTD) is an adverse birth outcome associated with increased infant mortality and negative lifelong health consequences. PTD may be the result of interactions between genetics and maternal/fetal environmental factors including smoking exposure (SMK). A common deletion in the GSTT1 gene was previously reported to affect birth outcomes in smokers. In this study, we dissect the associations among SMK, birth outcomes, and copy number variations (CNVs) in the GSTT1/GSTT2 region. A preterm birth case-control dataset of 1937 mothers was part of the GENEVA preterm birth study, which included genome-wide genotyping used to identify CNVs. We examined the association of SMK with birth outcomes, detected CNVs within the GSTT1/GSTT2 region using PennCNV, and examined associations of the identified CNVs with preterm birth and with birth weight (BW) in full term birth controls, including interactions with SMK. Finally, we tested the association of CNVs in GSTT1/GSTT2 with SMK. We confirmed the association of smoking with low BW and PTD. We identified 2 CNVs in GSTT2 (GSTT2(a) and GSTT2(b)), 1 CNV in GSTTP1 and 2 CNVs in GSTT1 (GSTT1(a) and GSTT1(b)). The GSTT2(a) deletion was associated with reduced BW (−284 g, p = 2.50E-7) in smokers, and was more common in smokers [odds ratio(OR) = 1.30, p = 0.04]. We found that the size of the reported common deletion CNV in GSTT1 was larger than previously shown. The GSTTP1 and GSTT1(b) null genotypes were in high linkage disequilibrium (LD) (D′ = 0.89) and less common in smokers (OR = 0.68, p = 0.019 and OR = 0.73, p = 0.055, respectively). These two deletions were in partial LD with GSTT2(a) and GSTT2(b) duplications. All 5 CNVs seem to be associated with increased risk of preterm birth before 35 completed weeks. CNVs in the GSTTT1/GSTT2 region appear associated with low BW and PTD outcomes, but LD complicated these CNVs in GSTT1/GSTT2. In genetic association studies of BW, multiple CNVs in this region need to be investigated instead of a single polymorphism. Frontiers Media S.A. 2013-10-28 /pmc/articles/PMC3809558/ /pubmed/24194744 http://dx.doi.org/10.3389/fgene.2013.00196 Text en Copyright © 2013 Zheng, Feingold, Ryckman, Shaffer, Boyd, Feenstra, Melbye, Marazita, Murray and Cuenco. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zheng, Xiaojing
Feingold, Eleanor
Ryckman, Kelli K.
Shaffer, John R.
Boyd, Heather A.
Feenstra, Bjarke
Melbye, Mads
Marazita, Mary L.
Murray, Jeffrey C.
Cuenco, Karen T.
Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title_full Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title_fullStr Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title_full_unstemmed Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title_short Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
title_sort association of maternal cnvs in gstt1/gstt2 with smoking, preterm delivery, and low birth weight
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809558/
https://www.ncbi.nlm.nih.gov/pubmed/24194744
http://dx.doi.org/10.3389/fgene.2013.00196
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