Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth

Fara Behnia, Sasha E. Parets, Talar Kechichian, Huaizhi Yin, Eryn H. Dutta, George Saade, Alicia K. Smith, Ramkumar Menon

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

OBJECTIVE: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth.

STUDY DESIGN: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant.

RESULTS: Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL.

CONCLUSION: Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume212
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Premature Birth
DNA Methylation
Extraembryonic Membranes
Genes
Methylation
Autism Spectrum Disorder
Term Birth
Epigenomics
gamma-Aminobutyric Acid
Reverse Transcription
Longitudinal Studies
Analysis of Variance
Leukocytes
Western Blotting
Polymerase Chain Reaction
DNA

Keywords

  • epigenetics
  • hydroxymethylation
  • OXTR
  • programing

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fetal DNA methylation of autism spectrum disorders candidate genes : association with spontaneous preterm birth. / Behnia, Fara; Parets, Sasha E.; Kechichian, Talar; Yin, Huaizhi; Dutta, Eryn H.; Saade, George; Smith, Alicia K.; Menon, Ramkumar.

In: American Journal of Obstetrics and Gynecology, Vol. 212, No. 4, 01.04.2015.

Research output: Contribution to journalArticle

Behnia, Fara ; Parets, Sasha E. ; Kechichian, Talar ; Yin, Huaizhi ; Dutta, Eryn H. ; Saade, George ; Smith, Alicia K. ; Menon, Ramkumar. / Fetal DNA methylation of autism spectrum disorders candidate genes : association with spontaneous preterm birth. In: American Journal of Obstetrics and Gynecology. 2015 ; Vol. 212, No. 4.
@article{481c14caead34108986c7882235a26a2,
title = "Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth",
abstract = "OBJECTIVE: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth.STUDY DESIGN: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant.RESULTS: Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL.CONCLUSION: Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies.",
keywords = "epigenetics, hydroxymethylation, OXTR, programing",
author = "Fara Behnia and Parets, {Sasha E.} and Talar Kechichian and Huaizhi Yin and Dutta, {Eryn H.} and George Saade and Smith, {Alicia K.} and Ramkumar Menon",
year = "2015",
month = "4",
day = "1",
doi = "10.1016/j.ajog.2015.02.011",
language = "English (US)",
volume = "212",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Fetal DNA methylation of autism spectrum disorders candidate genes

T2 - association with spontaneous preterm birth

AU - Behnia, Fara

AU - Parets, Sasha E.

AU - Kechichian, Talar

AU - Yin, Huaizhi

AU - Dutta, Eryn H.

AU - Saade, George

AU - Smith, Alicia K.

AU - Menon, Ramkumar

PY - 2015/4/1

Y1 - 2015/4/1

N2 - OBJECTIVE: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth.STUDY DESIGN: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant.RESULTS: Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL.CONCLUSION: Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies.

AB - OBJECTIVE: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth.STUDY DESIGN: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant.RESULTS: Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL.CONCLUSION: Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies.

KW - epigenetics

KW - hydroxymethylation

KW - OXTR

KW - programing

UR - http://www.scopus.com/inward/record.url?scp=84930745730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930745730&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2015.02.011

DO - 10.1016/j.ajog.2015.02.011

M3 - Article

C2 - 25687563

AN - SCOPUS:84930400258

VL - 212

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 4

ER -