Alleles and haplotypes of the estrogen receptor alpha gene are associated with an increased risk of spontaneous abortion

ObjectiveTo investigate whether polymorphisms in estrogen receptor alpha (ERα) or beta (ERβ) genes are associated with a risk of miscarriage.DesignA retrospectively analyzed, prospectively obtained database of cases and controls.SettingUniversity 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 ERα gene, and two SNPs located in intron 2 (C>T) and intron 8 (G>A) for the ERβ 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 ERα 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 ERβ gene.