Relationship between multiple genetic polymorphisms and hypertensive disorder in pregnancy

S146 SMFM Abstracts 468 ENDOTHELIUM -DEPENDENT AND -INDEPENDENT VASODILATATION IN PREECLAMPSIA AND HELLP SYNDROME JUDITH BLAAUW1, MARIA G. VAN PAMPUS1, GERHARD RAKHORST2, JAN G. AARNOUDSE1, 1University Medical Center Groningen, Obstetrics and Gynaecology, Groningen, Netherlands, 2 University Medical Center Groningen, Biomedical Engineering, Groningen, Netherlands OBJECTIVE: Systemic vascular dysfunction is thought to play an important role in preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Vasodilatory reactivity was found to be different in women with PE compared to HELLP syndrome, thereby suggesting different alterations of the vasculature (Fisher et al, AJOG 2000). We studied endothelium-dependent and -independent microvascular reactivity in women with PE, with and without HELLP syndrome. STUDY DESIGN: Skin perfusion, denoted as flux, was measured on the middle finger using laser Doppler perfusion monitoring in 5 pregnant women with PE, in 7 pregnant women with HELLP syndrome, in 12 women with a recent history of PE, and in 13 women with a recent history of HELLP syndrome. Postpartum measurements were performed during a time period of 3-11 months after delivery. Endothelium-dependent and -independent vasodilatation of the skin microcirculation was induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Microvascular vasodilatation was calculated as percentage increase from baseline to plateau flux. RESULTS: For both pregnancy and postpartum studies, clinical characteristics such as maternal age, body mass index and blood pressures were similar between the 2 groups. No significant differences in baseline and plateau fluxes, or in ACh-mediated vasodilatation were noticed. Although SNP-mediated vasodilatation in HELLP syndrome during pregnancy was higher, it did not reach statistical significance (table, meanG SEM).

470 RELATIONSHIP BETWEEN MULTIPLE GENETIC POLYMORPHISMS AND HYPERTENSIVE DISORDER IN PREGNANCY JONG KWAN JUN1, HYUN SOO PARK1, CHA-HUI LEE1, SOON-SUP SHIM1, JOONG SHIN PARK1, BO HYUN YOON1, 1Seoul National Unversity College of Medicine, Department of Obstetrics and Gynecology, Seoul, South Korea OBJECTIVE: Hypertensive disorder of pregnancy has a wide spectrum of clinical manifestations which are controlled by several genes. We genotyped 3 polymorphic sites of cystathione beta-synthase(CBS) G9276A, manganese superoxide dismutase(MnSOD) Val(-9)Ala and vascular endothelial growth factor(VEGF) C936T and examined whether they play a role in the development of hypertension during pregnancy. STUDY DESIGN: The subjects were 294 cases complicated by hypertensive disorder of pregnancy and 144 controls without complications. The medical records were reviewed. Cases were categorized according to the classification suggested by National High Blood Pressure Education Program Working Group. Maternal CBS G9276A, MnSOD Val(-9)Ala and VEGF C936T was determined by restriction fragment length polymorphism. Chi-square analysis was used to assess genotype and allele frequency differences. We applied haplotype analysis by HapAnalyzer for association study. RESULTS: All the study subjects were successfully genotyped and met Hardy-Weinberg equilibrium. Genotypes and allele frequencies of each polymorphism did not differ significantly between two groups. We evaluated 4 haplotypes (CBS G9276/MnSOD Val(-9)/VEGF C936, CBS G9276/MnSOD Val(-9)/VEGF T936, CBS A9276/MnSOD Val(-9)/VEGF C936, CBS G9276/ MnSOD Ala(-9)/VEGF C936). However, all showed no significant results. CONCLUSION: These three polymorphic sites may not be involved in the development of hypertensive disorder during pregnancy. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.513

CONCLUSION: Microvascular reactivity is similar between women with PE, with or without HELLP syndrome. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.511

469 PREECLAMPSIA AND SCD30 JUAN PEDRO KUSANOVIC1, JIMMY ESPINOZA2, SONIA HASSAN2, FRANCESCA GOTSCH1, OFFER EREZ1, NANDOR GABOR THAN1, SAMUEL EDWIN1, SHALI MAZAKI-TOVI2, LARA FRIEL2, POOJA MITTAL2, BO HYUN YOON3, ROBERTO ROMERO1, 1Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan, 2Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, 3 Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Seoul, South Korea OBJECTIVE: Preeclampsia (PE) is characterized by exaggerated intravascular inflammation and a predominantly Th1-biased immune response. There is controversy about the Th2 response in PE. CD30, a member of the tumor necrosis factor receptor superfamily, is preferentially expressed in vitro and in vivo by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is considered a marker for a Th2 immune response. The objective of this study was to determine the maternal serum concentration of sCD30 in patients with PE. STUDY DESIGN: This cross-sectional study included patients in the following groups: 1) non-pregnant women (n=20); 2) normal pregnancy (n=61); 3) PE (n=92); and 4) patients who delivered a small for gestational age (SGA) neonate (n=41). Maternal serum concentration of sCD30 was measured by specific and sensitive enzyme-linked immunoassays. Non-parametric tests were used for comparisons. A p value !0.05 was considered statistically significant. RESULTS: 1) Patients with PE had a significantly lower median serum concentration of sCD30 than normal pregnant women [median: 24.9 U/ml (range: 7.6-71.2) vs. median: 32.4 U/ml (range: 12.6-74.9); p!0.001]; 2) In contrast, SGA was not associated with a change in the maternal serum concentration of sCD30 [SGA median: 29.3 U/ml (range: 7.1-864.4) vs. normal pregnancy median: 32.4 U/ml (range: 12.6-74.9), respectively; p=0.1]; 3) Pregnancy was not associated with a change in the sCD30 serum concentrations [non-pregnant median: 32.4 U/ml (range: 12.6-74.9) vs. pregnant median: 26.8 U/ml (range: 18.7-195.1); p=0.5]; 4) There was no correlation between maternal serum sCD30 concentration and gestational age (20-38 weeks) in normal pregnant women. CONCLUSION: 1) Patients with PE had a significantly lower serum concentration of sCD30 than normal pregnant women; 2) This finding is consistent with the view that PE is associated with a polarized Th1 immune response through a decrease in Th2 response. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.512

471 PLACENTAL BUT NOT MATERNAL BUCCAL FAS GENE A-651G POLYMORPHISM IS ASSOCIATED WITH PREECLAMPSIA JOHN NGUYEN1, LANCE PARTON2, CHAU PHAM3, JUSTIN PETROCELLI3, ROYLAND ROBINSON4, CHAUR-DONG HSU1, 1New York Medical College-Westchester Medical Center, Obstetrics and Gynecology, Valhalla, New York, 2New York Medical College-Westchester Medical Center, Pediatrics, Valhalla, New York, 3New York Medical College 10595, New York, 4New York Medical College-Westchester Medical Center, Obstetrics and Gynecology, Vahalla, New York OBJECTIVE: We previously reported an elevated serum soluble Fas was associated with preeclampsia. We sought to determine if the frequencies for placental and/or maternal single nucleotide polymorphisms (SNPs) of Fas gene A-651G were altered in preeclamptic pregnancy. STUDY DESIGN: Thirteen pregnant women with preeclampsia and 25 normotensive pregnant women were studied. Preeclampsia was defined as proteinuric hypertension. DNA was extracted from maternal buccal swabs as well as from placental tissue. Polymorphisms of these DNA samples were subjected to allelic discrimination using real-time PCR and specific probes (Taqman probes, ABI). SNPs for Fas A-651G were analyzed. Statistical significance was tested using t-tests for demographic data and Chi-square analysis for genotype/allele data, with significance achieved at P ! 0.05. RESULTS: There were no significant differences in demographic data except gestational age between two groups. Preeclamptic placentas expressed significantly more genotype of GG and AG of Fas SNP (-651) than normotensives. In contrast, normotensive placentas expressed significantly more genotype of AA of Fas SNP (-651) [p=0.04]. The allele frequencies of the Fas SNP (-651) in preeclamptic placenta were 0.58 and 0.42 for G and A, respectively, as compared to 0.32 and 0.68, respectively, in placentas from normotensive pregnancies (P=0.05). However, there were no significant differences in maternal genotype as well as allele frequencies of Fas SNP (-651) between preeclampsia and normotensives. CONCLUSION: Our findings further indicate Fas gene might play an important role in the pathogenesis of preeclampsia. Altered allele frequencies as well as genotype of the Fas SNP (-651) in preeclamptic placentas but not in maternal buccal DNA suggests preeclampsia is a trophoblastic disorder. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.514