Fetal genetic polymorphisms associated with estrogen levels and sex-hormone-binding globulin and fetal growth restriction

摘要

Background: Intrauterine fetal growth restriction is a multifactorial disorder, and its etiology includes both environmental and genetic components. Consistent positive correlations between pregnancy estrogens and fetal size have been demonstrated; and a decrease in serum estradiol levels has been found in women with fetal growth restriction. Aims: We aimed to investigate whether fetal genetic polymorphisms associated with estradiol levels and sex-hormone-binding globulin (SHBG) affected fetal growth and pregnancy duration. Methods: We conducted a prospective cohort study of 228 mother-newborn pairs delivered singleton live births in Sapporo, Japan. Twenty-nine single nucleotide polymorphisms (SNPs), which were reported to be associated with circulating estradiol and SHBG in recent genome-wide association studies (GWAS), were detected in Japanese newborns. Multiple logistic regression and linear regression models were used to evaluate the associations between fetal genotypes and intrauterine fetal growth restriction (IUGR, defined as birth weight ＜10th percentile) and birth weight with adjustments for maternal age, parity, smoking status and alcohol use during pregnancy and infant gender. Results: The odds ratio (OR) for the risk of IUGR, in fetal AA and AT genotype groups in rs402675 (3p26.3 between CNTN6 and RPL23AP38) were 193.1 (95% confidence interval [CI], 5.0-7,354.8) and 13.9 (95% CI, 2.9-66.3) compared to the TT genotype group, respectively. The estimated reductions in birth weight were 673 g (standard error [SE], 221 g) and 132 g (SE, 66 g) for the AA and AT genotype groups, respectively. Conclusions: Our findings suggest that rs402675 in 3p26.3 region may be a susceptible marker to IUGR in a Japanese population.