449 HUMAN TELOMERASE REVERSE TRANSCRIPTASE (HTERT) MRNA EXPRESSION IN HYPERTENSIVE DISORDERS OF PREGNANCY YALIXIONG 1 , DAN LIEBERMANN 2 , ELIJ HOLTZMAN 3 , BARBARA HOFFMAN 2 , STACEY JERONIS 1 , SARMINA HASSAN 1 , ENRIQUE HERNÁNDEZ 1 , OSSIE GEIFMAN-HOLTZMAN 1 , 1 Temple University School of Medicine, Temple University, Obstetrics & Gynecology, Philadelphia, Pennsylvania, 2 Temple University School of Medicine, Temple University, Department of Biochemistry, Fels Institute, Philadelphia, Pennsylvania, 3 Sheba Medical Center, Tel-Aviv Uni- versity, Israel, Nephrology and Hypertension Unit, Ramat-Gan, Israel OBJECTIVE: To assess hTERT mRNA levels and telomerase activity in different categories of hypertensive disease in pregnancy. STUDY DESIGN: Fresh placental biopsies were collected from 60 patients: the preeclampsia study group, 32 pregnant patients (8 term (T) and 24 preterm (PT) gestation) and non-preeclampsia, control group, 29 pregnant patients (16 T and 13 PT). TotalRNA was isolated from placenta tissue and reversely transcribed to c-DNA. The hTERT mRNA relative expression level was detected with a probe- specific real-time quantitative PCR assay using -actin as the reference gene. Sta- tistical analysis was performed using the student t test. Parallel experiments to detect the telomerase activity were also employed with the TRAPeze gel-based te- lomerase detection assay: telomerase from each placental sample was isolated and applied to add telomeric repeats (GGTTAG) onto the 3= end of a substrate oligo- nucleotide. The extended products were amplified by PCR and the telomerase activity was determined by the size of the extended product with PAGE gel electro- phoresis. RESULTS: The ratio of average hTERT mRNA levels in the study group were higher than those in the control group in both preterm (1.71 versus 0.88, p⬍0.05) and term placentas (1.66 versus 1.15, p⬍0.05). In the study group, the HELLP cases and the severe preeclampsia cases had the highest average ratios of hTERT mRNA levels: 1.81,1.80 respectively. The average ratios of eclamptic and preeclamptic mRNA levels were 1.76 and 1.65. In both the preeclamptic (ratio: 1.78 versus 1.54, p⬍0.05) and control groups (ratio: 1.13 versus 0.93, p⬍0.05), hTERT mRNA levels were higher in the placentas obtained from patients with Body-mass index (BMI) above 30 compared with patients with lower BMI. The telomerase activity differ- ences were not detected using TRAPeze gel-based telomerase detection assay. CONCLUSION: This work provides novel data on telomerase biology which cor- relates the elevated hTERT mRNA expression with the progressive clinical mani- festations of preeclampsia 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.468 450 THE GADD45-P38 STRESS RESPONSE PATHWAY IN PREECLAMPSIA YALIXIONG 1 , DAN LIEBERMANN 2 , BARBARA HOFFMAN 2 , ELI J HOLTZMAN 3 , JENNIFER TRONT 2 , STACEY JERONIS 1 , ENRIQUE HERNÁNDEZ 1 , OSSIE GEIFMAN-HOLTZMAN 1 , 1 Temple Uni- versity School of Medicine, Temple University, Obstetrics & Gynecology, Philadel- phia, Pennsylvania, 2 Fels Institute, Temple University, Department of Biochemis- try,Temple University School of Medicine, Philadelphia, Pennsylvania, 3 Sheba Medical Center, Tel-Aviv University, Israel, Nephrology and Hypertension Unit, Ramat-Gan, Israel OBJECTIVE: To examine the role of growth arrest and DNA damage-inducible genes—Gadd45a, b and g and their downstream signal pathway activation in pre- eclampsia. STUDY DESIGN: Fresh placental biopsies were collected from 60 patients: the preeclampsia study group, 32 pregnant patients (8 term (T) and 24 preterm (PT) gestations) and non-preeclampsia, control group, 29 pregnant patients (16 T and 13 PT). Total RNA and total protein were isolated from the placenta. The RNA was reversely transcribed to c-DNA. The mRNA levels of Gadd45a, Gadd45b and Gadd45g were detected with a probe-specific real-time quantitative PCR assay us- ing -actin as the reference gene. Crossing point (Cp) values were obtained during the PCR amplification process and the relative expression levels of target genes were calculated as 2(Cp target gene &endash;Cp reference gene). Statistical analysis was performed using the student t test. Protein levels of Gadd45a and MAPK signal pathway genes--phospo-p38, phospho-JNK, and phospo-Mkk3/Mkk6 were as- sessed by western blot with specific antibodies. Total P38, total JNK and total MKK3 proteins were used as loading control. RESULTS: The average expression level of Gadd45a mRNA in the study group was 2.60 fold versus control (p⬍0.05). Both the Gadd45b mRNA and Gadd45g mRNA levels were increased in preeclamptic cases but were not statistically signif- icant. The protein level of Gadd45a was also elevated in the study group. Phosphor- ylated p38 protein was increased in the preeclamptic cases while there was no expressional difference of phospho-JNK protein in both groups. P38 activation in the study group was confirmed by the increased of phosphorylated MKK3, an upstream regulator modulating the activation of p38. CONCLUSION: Gadd45 mediated P38 activation plays an important role in in- flammation, immunological processes and the balance between survival and apo- ptosis. This study, thus,provides a novel evidence that links placental stress to pathological changes in preeclampsia via the Gadd45-p38 stress response pathway. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.469 451 ARE GENE POLYMORPHISM & CONCENTRATION OF UROTENSIN II AS PREECLAMPSIA IN KOREAN WOMEN? SOO-JEONG LEE 1 , BOK-KYUNG JUNG 1 , JAE- YOON SHIM 1 , SUNG-HUN NA 1 , HYE-SUNG WON 1 , PIL RYANG LEE 1 , AHM KIM 1 , 1 University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetric Gynecology, Seoul, South Korea OBJECTIVE: To evaluate potential relationships between urotensin II (UT gene polymorphisms and preeclampsia in Korean women STUDY DESIGN: A total of 253 participants, 109 with preeclampsia and 144 healthy pregnant controls, were enrolled in the study. Peripheral blood was ob- tained from all women and the genomic DNA was isolated. Using the real time polymerase chain reaction with the Taqman genotyping assay method, -605 polymorphisms in the 3=-untranslated region of the UTS2 gene (rs 228648) genotyped. Additionally, the UTS2 concentrations in mid-trimester & 3rd trim ter venous blood of 17 patients with preeclampsia were measured. RESULTS: When the preeclampsia group and the control group were com- pared, the distribution of genotypes of the -605G/A polymorphism and carri rate of 605A allele was not different (OR⫽0.85, 95% CI: 0.59-1.23). In domin model,carriersof the A allele werenot frequent in preeclamptic women. (OR⫽0.75, 95% CI: 0.45-1.23). Logistic regression analysis of the UTS2 geno and clinical parameters such as age, body mass index, educational status, n sex showed that carriage of the -605G allele to be less frequent in preeclam patients than in controls (adjusted OR⫽0.95, 95% CI:0.64-1.39). In dominant model, carriers of the A allele were not frequent in preeclamptic women. (ad OR⫽0.76, 95% CI: 0.45-1.30). In UTS2 concentrations of preeclamptic women, UTS2 gene -605G/A polymo phism statistically had no significant effect on any of the urotention II conce tions of the mid-trimester & 3rd trimester (Mid-trimester GG (n⫽10)0.14⫽0.0 ng/ml vs GA (n⫽4) 0.13⫽0.05 ng/ml vs AA (n⫽3) 0.15⫽0.07 ng/ml, p⬎0.05; 3r trimester GG (n⫽10) 0.15⫽0.06 ng/ml vs GA (n⫽4) 0.15⫽0.06 ng/ml vs AA (n⫽ 0.13⫽0.01 ng/ml, p⬎0.05). CONCLUSION: The present study demonstrates no relationship betwee gene -605G/A polymorphism and the susceptibility to developing preeclamp Korean women. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.470 452 ARGINASE ACTIVITY IS INCREASED WITH HELLP SYNDROME BUTNOTWITH PREECLAMPSIA AT TERMARUNDHATHI JEYABALAN 1 , AUGUSTINE RAJAKUMAR 1 , STACY MCGONIGAL 1 , NINA MARKOVIC 2 , CARL HUBEL 1 , SIDNEY MORRIS 3 , 1 University of Pittsburgh, Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, P sylvania, 2 University of Pittsburgh, Epidemiology, Pittsburgh, Pennsylvania, 3 Uni- versity of Pittsburgh, Molecular Genetics and Biochemistry, Pittsburgh, Penn vania OBJECTIVE: Normal pregnancy is a state of systemic vasodilation media part by nitric oxide (NO). Reduced NO bioavailability may be responsible for abnormal vascular adaptations to pregnancy and pathologic pregnancy stat as preeclampsia. NO synthesis is dependent on the supply of L-arginine, a s for both arginase(s) and NO synthase(s). Upregulation of arginase activity r NO bioavailability by competing for L-arginine and has been implicated in th pathophysiology of several vascular disorders. The aim of this study was to mine whether plasma arginase activity is elevated in HELLP syndrome or pr eclampsia compared to normal pregnancies. STUDY DESIGN: We conducted a case-control study of 8 women with H syndrome and 15 with preeclampsia without HELLP, with each case matche normal pregnancy (control) subject based on gestational age at sample coll race and parity. Plasma arginase activity was determined as the conversion labeled L-arginine to 14C-labeled urea. Data are presented as mean ⫽ SE and analyzed by Wilcoxon rank sum. RESULTS: Baseline demographic characteristics were similar in all grou cept for the earlier gestational age at delivery in women with HELLP syndro Plasma arginase activity was nearly 14-fold higher in women with HELLP syn drome compared to gestational age matched controls (0.83 ⫽ 0.29 vs 0.06 ⫽ nmol/ml/minute, n⫽8 per group,p⫽0.007).Women with preeclampsia had higher plasma arginase activity compared to controls (0.31 ⫽ 0.07 vs 0.2 ⫽ 0 nmol/ml/minute, n⫽15 per group)but this wasnot statistically significant (p⫽0.14). The highest arginase activity was observed in the HELLP group. CONCLUSION: Plasma arginase activity is elevated in HELLP syndrome pared to uncomplicated pregnancies, but not in preeclampsia at term. Liver and hemolysis may lead to hepatic and erythrocyte arginase release (which L-arginine bioavailability) and erythrocyte hemoglobin (which scavenges NO sulting in reduced NO and endothelial dysfunction associated with HELLP sy drome. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.471 www.AJOG.org SMFM Abstracts Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology S133