title: Association of a maternal CD14 -159 gene polymorphism with preterm premature rupture of membranes and spontaneous preterm birth in multi-fetal pregnancies.
abstract: CD14, the major receptor for bacterial lipopolysaccharide (LPS) as well as other microbial antigens, is a component of the innate immune system. We hypothesized that a single nucleotide C>T polymorphism at position -159 in the CD14 gene that results in elevated CD14 production would influence susceptibility to preterm premature rupture of membranes (PPROM) and spontaneous preterm birth (SPTB) in multi-fetal pregnancies. DNA from 107 mother-twin and three mother-triplet pairs was analyzed. Pregnancy outcomes were obtained after completion of testing. CD14*T homozygosity was present in 39.3% of 28 women whose pregnancies ended with PPROM, as opposed to 18.1% of 72 pregnancies without a SPTB (P=0.03). There was no relation between the fetal CD14 genotype and PPROM. The likelihood ratio (LR) for PPROM was 2.2 for women homozygous for CD14*T. The LR increased to 3.3 and 3.6 if the CD14 polymorphism was present in combination with previously determined maternal polymorphisms in the genes coding for the inducible 70kDa heat shock protein (hsp70-2) and the interleukin-1 receptor antagonist (IL1RN), respectively. Thus, an enhanced maternal pro-inflammatory immune response to LPS may increase susceptibility to PPROM in multi-fetal pregnancies.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Kalish
authors.forename: Santosh
authors.initials: S
authors.lastname: Vardhana
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Normand
authors.forename: Meruka
authors.initials: M
authors.lastname: Gupta
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
mesh_terms: D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011272:Pregnancy, Multiple / Q000235:genetics*; D047928:Premature Birth / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D018950:Lipopolysaccharide Receptors; D012795:Sialoglycoproteins