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.

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

Setting: University hospital menopause unit.

Patient(s): 177 women with at least one spontaneous abortion and 442 controls with at least one live birth and no history of miscarriage.

Intervention(s): None.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.