727 Longitudinal evaluation of altered methylationin IL1 gene family in normal pregnancyWendy White1, Brian Brost1, Jonathan O’Brien1, ElizabethBaldwin1, William Watson1, Carl Rose1, Norman Davies1, ZhifuSun2, Stephen Turner3, Ramakrishna Edukula3, Vesna Garovic3

1Mayo Clinic College of Medicine, Maternal Fetal Medicine, Rochester,MN, 2Mayo Clinic College of Medicine, Biomedical Statistics andInformatics, Rochester, MN, 3Mayo Clinic College of Medicine,Nephrology and Hypertension, Rochester, MNOBJECTIVE: The Interleukin 1 family contains Interleukin 1alpha(IL1a), Interleukin 1beta (IL1b), IL1 receptor antagonist (IL1RA) andtwo receptors ILR1 and 2. These are important proinflammatory me-diators in the establishment/ maintenance of normal pregnancy.STUDY DESIGN: The methylation profiles of the IL1 family (10 CpGsites in 5 genes) were characterized in maternal DNA from bloodlongitudinally in 14 women at �16 weeks, at delivery and postpartum(n�42) and in 14 nulligravid women. All patients were non-smokers,matched for age and BMI. Genomic DNA was derived from buffycoat, purified, bisulfite modified and run on the Illumina MethylationAssay platform. Mean methylation levels at each site were comparedusing a Students or paired t-test. Serum IL1b levels were measured byhigh sensitivity ELISA.RESULTS: The mean beta values (methylation %) at 10 CpG sites in 5IL1 genes are shown for each time point and for the nulligravid con-trols in the table below; values in bold represent statistically significantdifferences between pregnant and non-pregnant groups. Methylationpatterns are similar in both non-pregnant groups - postpartum andnulligravid. Methylation levels in the ILRA and IL1R1 do not changewith pregnancy. IL1a, IL1b, and IL1R2 become less methylated inearly pregnancy compared with postpartum levels (p�0.0005;p�0.0007; p�0.004/p�0.007) or nulligravid controls (p�0.03;p�0.006; p�0.00002/p�0.02) and hypomethylation persists or in-creases at delivery. Serum IL1 beta levels are higher in early pregnancy(mean 0.108 pg/mL) compared with normal values from the literature(� 0.05 pg/mL).CONCLUSION: Early normal pregnancy is associated with decreasedmethylation in IL1a, IL1b and ILR2 compared with non-pregnancylevels, which are the same regardless of parity. ILRA and ILR1 areunchanged. Serum IL1b levels, usually non-detectible in healthy con-trols, are increased in our early pregnancy cohort. Altered methylationin IL1 genes at different gestational time points may result in increasedexpression as demonstrated by increased IL1b serum levels associatedwith early pregnancy.

728 Methylation altered in IL1 family of genesin maternal DNA in preeclamptic versus normotensivepregnancy at time of deliveryWendy White1, Brian Brost1, Jonathan O’Brien1, ElizabethBaldwin1, William Watson1, Carl Rose1, Norman Davies1,Zhifu Sun2, Stephen Turner3, Vesna Garovic3

1Mayo Clinic College of Medicine, Maternal Fetal Medicine, Rochester,MN, 2Mayo Clinic College of Medicine, Biomedical Statistics andInformatics, Rochester, MN, 3Mayo Clinic College of Medicine,Nephrology and Hypertension, Rochester, MNOBJECTIVE: The Interleukin 1 family contains Interleukin 1 alpha(IL1a), Interleukin 1 beta (IL1b), IL1 receptor antagonist (IL1RA) andtwo receptors (IL1R1 and IL1R2). Alterations in the IL1 family havebeen associated with preeclampsia (PE). IL1a allelic variants havebeen correlated with PE, but changes in serum levels have not beenseen. Serum IL1b levels have been shown to be elevated in PE. In-creased expression of IL1RA has been shown in leukocytes from PEwomen. DNA methylation is an epigenetic mechanism that can con-trol gene expression. We sought to characterize the methylation pat-terns of 5 IL1 genes in maternal DNA in preeclamptic and normoten-sive pregnancies at the time of delivery.STUDY DESIGN: The methylation profiles of the IL1 family (10 CpGsites in 5 genes) were characterized in maternal leukocyte DNA fromblood in 14 normotensive (NT) women and in 14 PE cases at the timeof delivery. PE was diagnosed based on ACOG criteria. All patientswere non-smokers, primigravidae and were matched for age and BMI.Genomic DNA was derived from buffy coat, purified, and bisulfitemodified then run on the Illumina Methylation Assay platform. Meanmethylation levels at each CpG site were compared using a Studentst-test.RESULTS: Key CpG sites in the genes for IL1a (0.48 v. 0.44; p�0.01)and IL1b (0.27 v. 0.24; p�0.03; 0.22 v. 0.19; p�0.05) showed in-creased methylation in PE as compared with NT pregnancies at thetime of delivery. Decreased methylation in IL1R1 (0.80 v. 0.83;p�0.03) was seen in PE. No significant difference was seen in meth-ylation patterns in IL1R2 and ILRA.CONCLUSION: Methylation at key CpG sites was altered in the IL1a andIL1b genes (increased) and IL1R1 gene (decreased) in women with PEcompared with NT women at the time of delivery. Increased methyl-ation can result in decreased gene expression; our results contrast withthe literature in terms of protein levels of IL1b in serum, while IL1aand IL1R1 levels have not been studied in PE. We postulate that in-creased methylation may represent an endogenous regulatory mech-anism to ameliorate the proinflammatory state of PE.

www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V

Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S323