Role of single nucleotide polymorphisms of cytokine genes in spontaneous preterm delivery.
Intra-amniotic infections are implicated in spontaneous preterm delivery (PTD). Certain genetic polymorphisms are associated with increased production of proinflammatory and/or decreased production of anti-inflammatory cytokines, thereby possibly promoting PTD. We determined the relationship between maternal and fetal cytokine gene polymorphisms with occurrence and severity of spontaneous PTD (PTD after spontaneous-onset preterm labor and/or preterm prelabor rupture of membranes) and their association with intrauterine inflammation and infection. DNA from buccal brushings of 80 preterm (gestation < 35 weeks) and 80 matched term mother-infant pairs was assayed for tumor necrosis factor alpha (TNF-alpha [-308G/A]), interferon-gamma (IFN-gamma [+874A/T]), interleukin-6 (IL-6 [-174C/G]), interleukin-10 (IL-10 [-1082G/A, -819C/T, -592C/A]), and transforming growth factor beta1 (TGF-beta1 [T/Ccodon10,G/Ccodon25]) by using polymerase chain reaction (PCR) with sequence-specific primers. The presence of histologic chorioamnionitis was determined for PTDs. Conditioned on maternal IFN-gamma genotypes, fetal high IFN-gamma producing allele (IFN-gamma[+874T]) was associated with spontaneous PTD (odds ratio = 2.3 [1.2-4.4]). Among preterm deliveries, maternal low TGF-beta1 (TGF-beta1 [codon10C]) producing genotypes correlated negatively with gestation. Fetal TNF-alpha (-308G) was significantly associated with histologic chorioamnionitis. Underlying genitourinary infections and/or inflammation were significantly associated with maternal and fetal IL-6 (-174G), fetal TNF-alpha (-308GG), and fetal IL-10 (-1082A). We conclude that certain fetal and maternal cytokine gene polymorphisms may be associated with occurrence and/or severity of spontaneous PTD and with intrauterine inflammation and infection.
Speer
Esther Monika
EM
University of Chicago Hospitals, Department of Pediatrics, Chicago, Illinois 60637, USA. espeer2208156@aol.com
Gentile
Deborah Ann
DA
Zeevi
Adriana
A
Pillage
Gina
G
Huo
Dezheng
D
Skoner
David Peter
DP
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000276:immunology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology; D007752:Obstetric Labor, Premature / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D017931:DNA Primers