Polymorphisms in thrombophilia and renin-angiotensin system pathways, preterm delivery, and evidence of placental hemorrhage

OBJECTIVE: The purpose of this study was to analyze functional polymorphisms in candidate genes (methylenetetrahydrofolate reductase [MTHFR]677C>T, MTHFR1298A>C, factor 5 1691G>A [FVL], and angiolensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD) STUDY DESIGN: We assessed maternal genotypes, pregnancy outcomes, and placental pathologic evidence among 560 white and 399 black women who were recruited at mid trimester into a prospective cohort study (1998-2004) Odds of dominant genotypes were calculated for PTDs with (n = 56) or without (n = 177) evidence of placental hemorrhage (referent = term) with the use of race-stratified polytomous logistic regression models RESULTS: Among white women, FVL GA/AA and AGT(-6) GA/AA were both associated with hemorrhage-related PTDs (odds ratio [OR], 4 8 95% confidence interval [CI], 1.6-14 2 and OR, 3 8: 95% CI, 1.3-10.5, respectively), but not other PTDs (ORs, 1.2 and 0 9, respectively). FVL GA/AA was associated with placental abruption (OR, 5 8; 95% Cl, 1.1-30) among white women. All results were null for MTHFR genotypes. CONCLUSION: FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs