Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.
OBJECTIVE
The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery.


METHODS
A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing.


RESULTS
The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P=.000148) and tissue inhibitor of metalloproteinase 2 (mother; P=.000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P=.004 and .007, respectively).


CONCLUSIONS
An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.
Romero
Roberto
R
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA. prbchiefstaff@med.wayne.edu
Velez Edwards
Digna R
DR
Kusanovic
Juan Pedro
JP
Hassan
Sonia S
SS
Mazaki-Tovi
Shali
S
Vaisbuch
Edi
E
Kim
Chong Jai
CJ
Chaiworapongsa
Tinnakorn
T
Pearce
Brad D
BD
Friel
Lara A
LA
Bartlett
Jacquelaine
J
Anant
Madan Kumar
MK
Salisbury
Benjamin A
BA
Vovis
Gerald F
GF
Lee
Min Seob
MS
Gomez
Ricardo
R
Behnke
Ernesto
E
Oyarzun
Enrique
E
Tromp
Gerard
G
Williams
Scott M
SM
Menon
Ramkumar
R
D000328:Adult; D016022:Case-Control Studies; D002677:Chile; D002821:Chorioamnionitis / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D055815:Young Adult
D019947:Receptors, Interleukin-6
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