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
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.
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.
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.
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.