668: Endothelial function gene polymorphisms are associated with pregnancy outcomes, independent of placental vascular disease

PREGNANCY OUTCOMES, INDEPENDENT OF PLACENTAL VASCULAR DISEASE MONIQUE CHIREAU, DAVID CROSSLIN, ELIZABETH HAUSER, ANDREW OLSHAN, SIQUN ZHENG, CAROLYN M SALAFIA, JOHN THORP, Duke University, Obstetrics and Gynecology, Durham, North Carolina, Duke University, Center for Human Genetics, Durham, North Carolina, University of North Carolina at Chapel Hill, Epidemiology, Chapel Hill, North Carolina, Wake Forest University-Baptist Medical Center, Center for Human Genomics, , North Carolina, Columbia-Presbyterian Coll. of Physicians and Surgeons, Pathology, New York, New York, University of North Carolina at Chapel Hill, Obstetrics and Gynecology, Chapel Hill, North Carolina OBJECTIVE: To determine whether single nucleotide polymorphisms (SNPs) in endothelial function genes are associated with timing of delivery and fetal growth, through the intermediate of placental vascular disease, measured by chronic inflammation (CI) or vascular pathology (VP) on placental histology. STUDY DESIGN: We performed a case-control study of the association between SNPs in endothelial function genes, VP or CI, and preterm birth (PTB) or smallfor-gestational-age (SGA) birth. Genotyping was carried out on 476 women from the Pregnancy, Infection and Nutrition Study at the University of North CarolinaChapel Hill, using MALDI-TOF. Genes studied were known to be associated with adult cardiovascular disease and included Apo A1 G75A, Apo A5 T1131C, ApoC3 C482T, endothelin-1 K198N, E-selectin A561C, ICAM-1 K469E, IL-6 G174C, MTHFR A222V, VEG-F C936T, and VEG-F C2568A. Placentas were scored by a placental pathologist. Univariate and multivariate logistic regression analyses were performed. RESULTS: 83% of women were White and 17% Black. 15.2% and 7% of births were preterm or SGA, respectively. VP was noted in 34% and CI in 17% of placentas. VP was associated with decreased risk for SGA independent of genotype. Among White women the ApoC3 SNP was associated with decreased risk for VP (p 0.04, OR 0.69, CI 0.483-0.989). In PTB models including genotype, placental histology and maternal characteristics, the EDT-1 K469E SNP was associated with decreased PTB risk (p 0.006, OR 0.54, CI 0.35-0.84), independent of VP or CI. CONCLUSION: VP is associated with decreased risk for SGA. The endothelin-1 K198Ar SNP appears to be associated with reduced risk of PTB, but not with VP or CI, suggesting that it does not act through the intermediate of placental vascular disease; our power to detect differences for CI was low given sample size. Geneenvironment interactions may modulate these associations. Future studies of associations between genotype and ethnicity need to more fully account for genetic variation.