A case-control study of membrane cofactor protein mutations in two populations of patients with early pregnancy loss

  • Heuser C
  • Eller A
  • Warren J
 et al. 
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Abstract

Mouse models have demonstrated a strong link between complement activation and pregnancy loss. The purpose of this study was to assess if mutations or polymorphisms in the complement regulatory gene membrane cofactor protein (MCP) are associated with recurrent miscarriage (RM) or sporadic fetal loss (FL). This was a case-control study comprising two different populations of cases and controls: subjects with recurrent miscarriage (RM) and controls and maternal-fetal pairs with early fetal loss (at 10-20 weeks' gestation) and controls. In the RM cases and controls, we studied maternal DNA extracted from either whole blood or saliva samples. In the FL cases and controls, fetal DNA was obtained from evacuated products of conception (cases) or cord blood (controls). Exons from the MCP gene, previously identified as having functional mutations, were amplified with flanking primers, purified, and sequenced. Sequences were analyzed against the published reference sequence, the presence of known mutations and polymorphisms and novel polymorphisms. We enrolled and obtained maternal DNA from 75 women with RM and 115 controls. In the FL group, we identified 33 cases and 37 controls. We detected the previously described A304V variant, but neither genotype nor allele frequencies differed significantly between cases and controls in any of the populations (RM, FL (maternal) or FL (fetal)). Although other variants and mutations in MCP were identified, no significant differences were found between the groups. Thus, we conclude that the A304V mutation in the MCP gene is not strongly associated with RM or FL. © 2011 Elsevier Ireland Ltd.

Author-supplied keywords

  • Complement
  • Fetal loss
  • Pregnancy loss
  • Recurrent miscarriage

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Authors

  • Cara C. Heuser

  • Alexandra G. Eller

  • Jennifer Warren

  • D. Ware Branch

  • Jane Salmon

  • Robert M. Silver

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