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32: Maternal and fetal factor V and methlyene tetrahydrofolate reductase (MTHFR) genotype and fetal/placental thrombotic and inflammatory lesions

      Objective

      To explore the relation between maternal and fetal variation in Factor V and MTHFR genes and histologic evidence of fetal/placental inflammatory and thrombotic lesions

      Study design

      In this prospective observational cohort of 111 women with singleton gestations DNA was extracted from maternal and cord blood from all subjects. Factor V and MTHFR genotype assays on all mom-baby pairs were performed on an Illumina® platform. Single nucleotide polymorphism (SNP) selection was made using a linkage disequilibrium (LD) bin approach. LD bins are composed of SNPs that are very highly correlated with each other, where a single tag SNP can be used to predict the genotypes of other SNPs in the bin. Fifteen tagSNPs were selected in the MTHFR gene and 26 tagSNPs in the Factor V gene. All placentae were examined by a single blinded perinatal pathologist. The diagnoses of fetal/placental thrombosis and inflammation were made using the criteria of Redline et al.

      Results

      After adjustment for multiple comparisons, one fetal SNP in MTHFR (rs17421462) and one fetal SNP in Factor V (rs10489185) demonstrated highly significant association with thrombotic and inflammatory lesions. In a multivariable model with adjustment for maternal race, smoking, and bacterial vaginosis, carriage of these polymorphic alleles was strongly associated with thrombotic and inflammatory lesions (fetal rs17421462: odds ratio 4.2, p=0.02. fetal rs10489185: odds ratio 0.18, p=0.007). There was no evidence of statistical interaction between these two SNPs.

      Conclusion

      Fetal genetic variation in MTHFR and Factor V is strongly associated with histologic evidence of fetal/placental inflammation and thrombosis. These genotypic effects are independent of each other and other environmental covariates.