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 angiotensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD).


METHODS
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% CI, 1.1-30) among white women. All results were null for MTHFR genotypes.


CONCLUSIONS
FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs.
Gargano
Julia Warner
JW
Department of Epidemiology, College of Human Medicine, Michigan State University, East Lansing, MI 48823, USA.
Holzman
Claudia B
CB
Senagore
Patricia K
PK
Reuss
M Lynne
ML
Pathak
Dorothy R
DR
Friderici
Karen H
KH
Jernigan
Katherine
K
Fisher
Rachel
R
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010922:Placenta Diseases / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics; D055815:Young Adult
C095381:factor V Leiden; D000808:Angiotensinogen; D005165:Factor V; D042965:Methylenetetrahydrofolate Reductase (NADPH2)