Searching for Links between Endotoxin Exposure and Pregnancy Loss: CD14 Polymorphism in Idiopathic Recurrent Miscarriage

Abstract

Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of abortions in mice. In addition it has been proposed that gut-derived LPS of gram-negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD14 is one of the key molecules that mediates the effects of LPS. Promoter region polymorphism (-159C/T) in the CD14 gene is functionally important by regulating CD14 levels. High-producing CD14 genotype (TT) associates with deleterious effects of gut-derived LPS in hepatic cirrhosis in humans. It is not known whether women with IRM are genetically more prone to suffer from toxic effects of LPS. By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal controls of Finnish origin. There were no significant differences in the CD14 (-159C/T) allele or the genotype frequencies between the IRM women and the controls. However, there was a trend associating the presence of the T allele with increased odds of miscarriage. Although we were not able to find a statistically significant association between CD14 genotypes and IRM in our relatively small study population, a further study with a larger sample size is warranted to explore the role of high-producing CD14 genotypes in IRM. Also studies highlighting environmental LPS triggers and other intrinsic mediators of LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans.