Journal article
Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
Frontiers in genetics, Vol.4, pp.196-196
2013
DOI: 10.3389/fgene.2013.00196
PMCID: PMC3809558
PMID: 24194744
Abstract
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.
Details
- Title: Subtitle
- Association of maternal CNVs in GSTT1/GSTT2 with smoking, preterm delivery, and low birth weight
- Creators
- Xiaojing Zheng - Department of Biostatistics, Graduate School of Public Health, University of PittsburghEleanor Feingold - Department of Human Genetics, Graduate School of Public Health, University of PittsburghKelli K Ryckman - Department of Pediatrics, College of Medicine, University of IowaJohn R Shaffer - Department of Human Genetics, Graduate School of Public Health, University of PittsburghHeather A Boyd - Department of Epidemiology Research, Statens Serum InstitutBjarke Feenstra - Department of Epidemiology Research, Statens Serum InstitutMads Melbye - Department of Epidemiology Research, Statens Serum InstitutMary L Marazita - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of PittsburghJeffrey C Murray - Department of Pediatrics, College of Medicine, University of IowaKaren T Cuenco - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Frontiers in genetics, Vol.4, pp.196-196
- DOI
- 10.3389/fgene.2013.00196
- PMID
- 24194744
- PMCID
- PMC3809558
- NLM abbreviation
- Front Genet
- ISSN
- 1664-8021
- eISSN
- 1664-8021
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 2013
- Academic Unit
- Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9983996057602771
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