Microsomal epoxide hydrolase polymorphism and risk of spontaneous abortion

Abstract

We conducted a nested case-control study to examine the association of microsomal epoxide hydrolase polymorphism with spontaneous abortion. The analysis included 127 cases and 107 controls from a rural community in China. The prevalence of the homozygous wild-type (AA), the heterozygous variant (Aa), and the homozygous variant (aa) in exon 3 of epoxide hydrolase was 13.4%, 34.6%, and 52.0% in cases and 27.1%, 30.8%, and 42.1% in controls, respectively. In contrast, the variant genotypes in exon 4 of epoxide hydrolase were less frequent in cases than controls. Using women with genotype AA as the referent, the adjusted odds ratio of spontaneous abortion was 2.69 [95% confidence interval (CI) = 1.33-5.42] for those with genotype Aa or aa in exon 3; but it was 0.45 (95% CI = 0.22-0.94) for those with genotype Aa or aa in exon 4, indicating that the two variants have opposite associations with spontaneous abortion. The findings persisted after adjustment for age, education, parity, smoking, alcohol use, occupation, and pesticide exposure, as well as in subgroup analysis. Moreover, for the variant genotypes Aa or aa in exon 3, the odds ratio was twice as great in those cases with three or more spontaneous abortions than in those with fewer spontaneous abortions.

PIP: The possibility that the risk of spontaneous abortion associated with exposure to endogenous or exogenous substances is modified by genetic variation in metabolic detoxification activities was explored in a nested case-control study. The analysis included 127 cases and 107 controls from a rural community in China's Anhui Province. Prevalences of the homozygous wild type (AA), the heterozygous variant (Aa), and the homozygous variant (aa) in exon 3 of epoxide hydrolase were 13.4%, 34.6%, and 52.0%, respectively, in cases and 27.1%, 30.8%, and 42.1%, respectively, in controls. However, the variant genotypes in exon 4 were less frequent in cases than controls. When women with genotype AA were used as the reference group, the adjusted odds ratios of spontaneous abortion were 2.69 (95% confidence interval (CI), 1.33-5.42) in women with genotype Aa or aa in exon 3 and 0.45 (95% CI, 0.22-0.94) in those with genotype Aa or aa in exon 4. The finding that the two variants have opposite associations with spontaneous abortion persisted after adjustment for age, education, parity, smoking, alcohol use, occupation, and pesticide exposure as well as in subgroup analysis. For the variant genotypes Aa or aa in exon 3, the odds ratio was twice as great in cases with three or more spontaneous abortions (6.77; 95% CI, 0.80-57.00) than in those with under three such events (2.48; 95% CI, 1.21-5.07). The mechanism by which epoxide hydrolase polymorphisms influence a woman's spontaneous abortion risk remain uncertain. More widespread use of molecular genetic diagnostic tests in reproductive medicine has the potential to yield new insights into the etiology, mechanism, and risk of adverse reproductive outcomes.