Maternal IVS1-401 T allele of the estrogen receptor alpha is an independent predictor of late fetal loss.
OBJECTIVE
To investigate whether sequence variants in the gene encoding for estrogen receptor alpha (ER-alpha) are risk determinants for fetal loss.


METHODS
Case-control study.


METHODS
University medical center.


METHODS
One hundred four women with a history of fetal loss and 277 healthy women with at least one previous pregnancy and no previous fetal loss.


METHODS
None.


METHODS
The IVS1-401C/T polymorphism of the human ER-alpha, the G1691A mutation of the factor V gene (factor V Leiden), the G20210A mutation of the prothrombin gene, and the C677T polymorphism of the methylenetetrahydrofolate-reductase (MTHFR) gene were determined by polymerase chain reaction.


RESULTS
In the subgroup analysis of women with at least one late miscarriage (n = 70), the prevalences of the ER-alpha IVS1-401 T allele (T/T vs. C/C, odds ratio [OR]: 2.85, P=.018; T/T + C/T vs. C/C, OR: 2.28, P=.043) and of heterozygous factor V Leiden (OR, 3.2; P=.002) were significantly higher among women with late fetal loss than among healthy women. Carriers of both risk determinants have an at-least additive increase in risk for late abortions (OR, 7.0; P=.0004). The population of all late abortions that would be attributable to the genetic variants (population attributable risk) was 13.9% for factor V Leiden and 49.2% for the ER-alpha IVS1-401 T allele.


CONCLUSIONS
Women with the IVS1-401 T allele of the ER-alpha and/or factor V Leiden are at increased risk for late fetal loss.
Gerhardt
Andrea
A
Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Scharf
Rüdiger E
RE
Mikat-Drozdzynski
Barbara
B
Krüssel
Jan S
JS
Bender
Hans-Georg
HG
Zotz
Rainer B
RB
D000022:Abortion, Spontaneous / Q000235:genetics*; D000225:Adenine; D000483:Alleles; D016022:Case-Control Studies; D003596:Cytosine; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005165:Factor V / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006147:Guanine; D049669:History, 16th Century; D006801:Humans; D007438:Introns; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D013941:Thymine
D047628:Estrogen Receptor alpha; C095381:factor V Leiden; D006147:Guanine; D003596:Cytosine; D005165:Factor V; D000225:Adenine; D013941:Thymine