705: Polymorphisms of the glucocorticoid receptor gene NR3C1 and the association with birth weight and gestational age at delivery

Abstract

gene NR3C1 and the association with birth weight and gestational age at delivery Jennifer Wong, Yula Ma, Luca Lambertini, Andrea Weintraub, Joanne Stone Mount Sinai School of Medicine, Maternal Fetal Medicine, New York, NY, Mount Sinai School of Medicine, Department of Preventive Medicine, New York, NY, Mount Sinai School of Medicine, Pediatrics, New York, NY OBJECTIVE: To determine the association of glucocorticoid receptor gene NR3C1 single nucleotide polymorphisms (SNPs) with birth weight and prematurity. STUDY DESIGN: This was a single center, pilot study of 80 umbilical cord blood samples collected prospectively from singleton pregnancies. DNA was isolated from each blood sample. SNPs were genotyped by Taqman assay (rs6193, rs6194, rs6195, rs6196, rs6198, rs258751) and sequencing (rs6189, rs6190). Linear regression models were calculated for birth weight (BW) and gestational age at delivery (GAd). RESULTS: The rs6195 SNP was not polymorphic in our sample, and was therefore excluded from further statistical analysis. The average BW was 3330g [1930-4660g]. The average GAd was 39.5 weeks [3241.6] with only 3 deliveries occurring prior to 37 weeks. The BW linear regression model showed a significant correlation with preterm labor, vaginal delivery, maternal Asian ethnicity, and the rs6196 variant (p 0.01; r2 0.270). The rs6196 GG genotype was associated with a 761g reduction in BW (95% CI 125-1398; p 0.02). The GAd linear regression model of gestational age at delivery also showed a significant correlation with preterm labor, betamethasone administration, neonatal intensive care unit admission, as well as the rs6196 GG genotype (p 0.01; r2 0.476). In this regression, the GG genotype was associated with an earlier GAd (95% CI 0.92-0.99; p 0.01). None of the other SNPs analyzed showed any significant correlation with either outcome. CONCLUSION: The GG genotype of the rs6196 SNP of the glucocorticoid receptor gene NR3C1 is associated with both lower birth weight and earlier gestational age at delivery. These data are consistent with existing scientific literature that correlates this and other SNP phenotypes to lower weight, BMI, waist/hip ratio, and decreased insulin resistance. This glucocorticoid-resistant phenotype may ultimately be protective postnatally among hypercortisolemic premature infants. Given the results from this interim analysis, our investigation will continue with a focus on umbilical cord blood collections from premature infants.