Searching for links between endotoxin exposure and pregnancy loss: CD14 polymorphism in idiopathic recurrent miscarriage

PROBLEM: Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of abortions in mice. In addition it has been proposed that derived LPS of gram-negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD 14 is one of key molecules that mediates the effects of LPS. Promoter region polymorphism (-159C/T) in the CD14 gene is functionally 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 . METHOD OF STUDY: By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women IRM and in 127 normal controls of Finnish origin. RESULTS: There were no significant differences in the CD14 (-159C/T) allele or the genotype frequencies between the IRM and the controls. However, there was a trend associating the of the T allele with increased odds of miscarriage. CONCLUSIONS: 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 size is warranted to explore the role of high-producing CD 14 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.