Association of a maternal CD14 −159 gene polymorphism with preterm premature rupture of membranes and spontaneous preterm birth in multi-fetal pregnancies

• Published in: Journal of Reproductive Immunology 2006-06, Vol.70 (1), p.109-117
• Main Authors: Kalish, Robin B., Vardhana, Santosh, Normand, Neil J., Gupta, Meruka, Witkin, Steven S.
• Format: Article
• Language: English
• Subjects: 70 kDa heat shock protein; Biological and medical sciences; CD14; Diseases of mother, fetus and pregnancy; Female; Fetal Membranes, Premature Rupture - genetics; Genetic polymorphism; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 receptor antagonist; Lipopolysaccharide Receptors - genetics; Medical sciences; Multi-fetal pregnancies; Polymorphism, Genetic; PPROM; Pregnancy; Pregnancy, Multiple - genetics; Pregnancy. Fetus. Placenta; Premature Birth - genetics; Sialoglycoproteins - genetics
• ISSN: 0165-0378; 1872-7603; 1365-2567
• DOI: 10.1016/j.jri.2005.12.002

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 70 kDa 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.