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

Abstract

Objective: To investigate whether polymorphisms in estrogen receptor alpha (ERα) or beta (ERβ) 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 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. © 2010 American Society for Reproductive Medicine.