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Risk of miscarriage and a common variant of the estrogen receptor gene.

An inherited variant of the estrogen receptor gene was previously suggested to be a major determinant of a woman's risk of miscarriage. The authors tested this hypothesis in a case-control study of 29 women who had had two or more miscarriages and 29 women with no miscarriages. All of the women had given birth in North Carolina between 1987 and 1990. Estrogen receptor genotype was determined by direct sequencing of DNA. The gene variant that supposedly produced the risk was found to contain only a silent substitution at codon 87. Furthermore, instead of an odds ratio of 25 (predicted by the previous study), the odds ratio found was 1.8 (95% confidence interval 0.3-11). For a hypothesis which now lacks biologic plausibility, this weak association provides little reason for further investigation.