Alleles and haplotypes of the estrogen receptor alpha gene are associated with an increased risk of spontaneous abortion.
OBJECTIVE
To investigate whether polymorphisms in estrogen receptor alpha (ERalpha) or beta (ERbeta) genes are associated with a risk of miscarriage.


METHODS
A retrospectively analyzed, prospectively obtained database of cases and controls.


METHODS
University hospital menopause unit.


METHODS
177 women with at least one spontaneous abortion and 442 controls with at least one live birth and no history of miscarriage.


METHODS
None.


METHODS
Genotype frequencies and odd ratios for abortion risk in cases and controls for four single nucleotide polymorphisms (SNPs) located in intron 1 (C>T and A>G), intron 4 (A>T), and exon 8 (T>C) for the ERalpha gene, and two SNPs located in intron 2 (C>T) and intron 8 (G>A) for the ERbeta gene.


RESULTS
A statistically significant association was found between spontaneous abortion and SNPs rs2234693 (C>T, defined by restriction enzyme PvuII) and rs9340799 (A>G, defined by restriction enzyme XbaI) in intron 1 of the ERalpha gene. The age-adjusted odds ratio for abortion risk was 1.29 for the TA haplotype (defined by PvuII-XbaI) with respect to the CG haplotype in women with at least one abortion, which increased to 1.9 in women with two or more abortions.


CONCLUSIONS
The TA haplotype defined by PvuII and XbaI was associated with an increased risk of reproductive loss. No association was found for the ERbeta gene.
Pineda
Begoña
B
Research Foundation, Hospital Clínico Universitario, Valencia, Spain.
Hermenegildo
Carlos
C
Tarín
Juan J
JJ
Laporta
Paz
P
Cano
Antonio
A
García-Pérez
Miguel Angel
MA
D000022:Abortion, Spontaneous / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta