p24. study of c677t methylene tetrahydrofolate reductase (mthfr) polymorphism in preeclampsia

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Hina Saeed Zuberi a , Rozina Sikandar c ( a Department of Biological & Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan, b Department of Com- munity Health Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan, c Department of Obstetrics & Gynaecology, Aga Khan University Hospital, Stadium Road, Karachi, Pakistan, d The Aga Khan Hospital for Women, Karimabad, Karachi, Pakistan, e Department of Pharmacology, Alfaisal University, Riyadh, Saudi Arabia) Objective: To test the hypothesis that preeclampsia (PE) can be predicted in primiparas early by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and pla- cental growth factor (PlGF). Methods: All normotensive primiparas attending antena- tal clinics of Aga Khan University Hospital and Aga Khan Hospital for Women, Karachi, Pakistan without any known risk factor for PE were invited to participate in the study. They were divided into two groups based on the develop- ment of PE. Blood samples of the participants were collected at 8–15; 16–22; 23–28; 29–34 weeks of pregnancy and a postnatal sample and were analyzed for sFlt-1 and PlGF. Results: 611 (46.7%) out of 1307 recruited primiparas completed the study according to the protocol. Out of these, 39 (6.4%) women developed PE. Difference in the serum sFlt- 1 was evident as early as up to 15 weeks of gestation. Higher levels of sFlt-1 were present in women who later developed PE. Relatively higher levels of PlGF were observed in non-PE women compared to PE women up to 22 weeks of gestation. However, after 23 weeks of pregnancy, PlGF levels increased in both Groups but less so in PE Group. ROC curve analysis showed that even in early pregnancy (<15 weeks of gesta- tion); sFlt-1 alone has the potential to predict PE with AUC, sensitivity and specificity of 0.81, 75.9 and 72.4, respectively. Conclusions: PE can be predicted in primiparas in early part of second trimester with serum sFlt-1 and in later part of second trimester with serum PlGF. doi:10.1016/j.preghy.2011.08.084 P25. Study of C677T methylene tetrahydrofolate reduc- tase (MTHFR) polymorphism in preeclampsia Andreia Matos a,f , Joana Ferreira a , Ana Portelinha b , Ana Sofia Cerdeira c , Jorge Braga c , Belmiro Patrício d,e , Irene Rebelo b,e , Manuel Bicho a,f , Claudia Marinho a,f ( a Genetic Laboratory, Centre of Endocrinology and Metabolism, Lisbon Medical School, Portugal, b Institute for Molecular and Cell Biology, University of Porto, Portugal, c Depart- ment of Obstetrics, Sto António Hospital, Porto, Portugal, d Department of Obstetrics and Gynecology, Porto Medi- cal School, S. João Hospital, Porto, Portugal, e Faculty of Pharmacy, Biochemical Department, University of Porto, Portugal, f Bento Rocha Cabral Institute, Lisbon, Portugal) Introduction: Methylenetetrahydrofolate reductase (MTHFR) seems to play a role in hypertension because of its influence on plasma Hcy levels (Homocysteine), second- ary to oxidative stress that inhibits the enzyme. Elevated plasma Hcy has been found in hypertensive patients and showed a positive correlation with blood pressure. It has been suggested that Hcy is involved in the promotion of platelet activation, hypercoagulability, oxidative stress, endothelial dysfunction, smooth muscle cell proliferation and oxidation and peroxidation of lipids. Some of these ef- fects are modified by NO availability. The T allele of the C677T MTHFR polymorphism reduces its activity and inhib- its the formation of 5-methyltetrahydrofolate decreasing the remethylation of Hcy to methionine and SAM important for epigenetic regulation of several genes including NO synthase. Objectives: To associate the C677T MTHFR polymorphism with preeclampsia and to study its relation with MPO (mie- loperoxidase), NO (nitric oxide), Nitrates and Nitrites concentrations. Materials and methods: We studied 63 women with his- tory of preenclampsia 3–6 years postpartum (PEW)- 35.4 ± 5.5 years; 26.9 ± 4.8 kg/m 2 and 59 controls with no history of pregnancy complications (NW)-35.0 ± 5.6 years; 25.4 ± 4.1 kg/m 2 . C677T MTHFR was studied by PCR-RFLP and biochemical parameters were measured using commer- cial available ELISA kits. Results: Genotype frequencies of C677T MTHFR were: NW (CC = 45.8%; CT = 44.0%; TT = 10.2%) and PEW (CC = 40.4%; CT = 56.4%; TT = 3.2%) and showed no differ- ences between the two studied groups (p = 0.477). The same happened with the distribution of MPO, NO, Nitrates and Ni- trites concentrations by C677T MTHFR polymorphism in women in general and in PEW and NW separately. Plasma MPO concentration is increased in PEW (87.3 ± 37.8 ng/ml vs 62.6 ± 33.0 ng/ml; p = 0.010). Conclusions: Although C677T MTHFR plays an important role in the control of MTHFR enzyme activity and this en- zyme is involved in Hcy metabolism, in this specific popula- tion, it did not seem to have an influence in the development of preeclampsia. In our study, it seems to have a decrease in TT frequency among PEW. These results may be justified if we consider that all these women took folic acid during pregnancy and that the decrease of Hcy levels by folate is more effective in homozygous for allele T. doi:10.1016/j.preghy.2011.08.085 P26. Increased inhibin A in severed preeclampsia/ eclampsia Y. Arisanti, M.I.A. Akbar, B. Wicaksono, A. Sulistyono, E.G. Dachlan, M.D. Angsar (Obstetric and Gynecology Depart- ment, Airlangga University Medical Faculty, Dr. Soetomo Hospital Surabaya, Indonesia) Objectives: Inhibin is a glycoprotein hormone of a heterodimer made up of an a-subunit and one of two distinct b-subunits, bA or bB that all three are produced by tropoblast cells where the function is to inhibit pituitary FSH release. Over this study we made assesment on maternal serum level of inhibin A, placental level and expression of inhibin A in severe pre-eclampsia. 284 Poster Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 1 (2011) 273–299

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Hina Saeed Zuberi a, Rozina Sikandar c (a Department ofBiological & Biomedical Sciences, Aga Khan University,Stadium Road, Karachi, Pakistan, b Department of Com-munity Health Sciences, Aga Khan University, StadiumRoad, Karachi, Pakistan, c Department of Obstetrics &Gynaecology, Aga Khan University Hospital, StadiumRoad, Karachi, Pakistan, d The Aga Khan Hospital forWomen, Karimabad, Karachi, Pakistan, e Department ofPharmacology, Alfaisal University, Riyadh, Saudi Arabia)

Objective: To test the hypothesis that preeclampsia (PE)can be predicted in primiparas early by measuring serumlevels of soluble fms-like tyrosine kinase-1 (sFlt-1) and pla-cental growth factor (PlGF).

Methods: All normotensive primiparas attending antena-tal clinics of Aga Khan University Hospital and Aga KhanHospital for Women, Karachi, Pakistan without any knownrisk factor for PE were invited to participate in the study.They were divided into two groups based on the develop-ment of PE. Blood samples of the participants were collectedat 8–15; 16–22; 23–28; 29–34 weeks of pregnancy and apostnatal sample and were analyzed for sFlt-1 and PlGF.

Results: 611 (46.7%) out of 1307 recruited primiparascompleted the study according to the protocol. Out of these,39 (6.4%) women developed PE. Difference in the serum sFlt-1 was evident as early as up to 15 weeks of gestation. Higherlevels of sFlt-1 were present in women who later developedPE. Relatively higher levels of PlGF were observed in non-PEwomen compared to PE women up to 22 weeks of gestation.However, after 23 weeks of pregnancy, PlGF levels increasedin both Groups but less so in PE Group. ROC curve analysisshowed that even in early pregnancy (<15 weeks of gesta-tion); sFlt-1 alone has the potential to predict PE withAUC, sensitivity and specificity of 0.81, 75.9 and 72.4,respectively.

Conclusions: PE can be predicted in primiparas in earlypart of second trimester with serum sFlt-1 and in later partof second trimester with serum PlGF.

doi:10.1016/j.preghy.2011.08.084

P25. Study of C677T methylene tetrahydrofolate reduc-tase (MTHFR) polymorphism in preeclampsiaAndreia Matos a,f, Joana Ferreira a, Ana Portelinha b, AnaSofia Cerdeira c, Jorge Braga c, Belmiro Patrício d,e, IreneRebelo b,e, Manuel Bicho a,f, Claudia Marinho a,f (a GeneticLaboratory, Centre of Endocrinology and Metabolism,Lisbon Medical School, Portugal, b Institute for Molecularand Cell Biology, University of Porto, Portugal, c Depart-ment of Obstetrics, Sto António Hospital, Porto, Portugal,d Department of Obstetrics and Gynecology, Porto Medi-cal School, S. João Hospital, Porto, Portugal, e Faculty ofPharmacy, Biochemical Department, University of Porto,Portugal, f Bento Rocha Cabral Institute, Lisbon, Portugal)

Introduction: Methylenetetrahydrofolate reductase(MTHFR) seems to play a role in hypertension because ofits influence on plasma Hcy levels (Homocysteine), second-ary to oxidative stress that inhibits the enzyme. Elevated

plasma Hcy has been found in hypertensive patients andshowed a positive correlation with blood pressure. It hasbeen suggested that Hcy is involved in the promotion ofplatelet activation, hypercoagulability, oxidative stress,endothelial dysfunction, smooth muscle cell proliferationand oxidation and peroxidation of lipids. Some of these ef-fects are modified by NO availability. The T allele of theC677T MTHFR polymorphism reduces its activity and inhib-its the formation of 5-methyltetrahydrofolate decreasing theremethylation of Hcy to methionine and SAM important forepigenetic regulation of several genes including NOsynthase.

Objectives: To associate the C677T MTHFR polymorphismwith preeclampsia and to study its relation with MPO (mie-loperoxidase), NO (nitric oxide), Nitrates and Nitritesconcentrations.

Materials and methods: We studied 63 women with his-tory of preenclampsia 3–6 years postpartum (PEW)-35.4 ± 5.5 years; 26.9 ± 4.8 kg/m2 and 59 controls with nohistory of pregnancy complications (NW)-35.0 ± 5.6 years;25.4 ± 4.1 kg/m2. C677T MTHFR was studied by PCR-RFLPand biochemical parameters were measured using commer-cial available ELISA kits.

Results: Genotype frequencies of C677T MTHFR were:NW (CC = 45.8%; CT = 44.0%; TT = 10.2%) and PEW(CC = 40.4%; CT = 56.4%; TT = 3.2%) and showed no differ-ences between the two studied groups (p = 0.477). The samehappened with the distribution of MPO, NO, Nitrates and Ni-trites concentrations by C677T MTHFR polymorphism inwomen in general and in PEW and NW separately. PlasmaMPO concentration is increased in PEW (87.3 ± 37.8 ng/mlvs 62.6 ± 33.0 ng/ml; p = 0.010).

Conclusions: Although C677T MTHFR plays an importantrole in the control of MTHFR enzyme activity and this en-zyme is involved in Hcy metabolism, in this specific popula-tion, it did not seem to have an influence in the developmentof preeclampsia. In our study, it seems to have a decrease inTT frequency among PEW. These results may be justified ifwe consider that all these women took folic acid duringpregnancy and that the decrease of Hcy levels by folate ismore effective in homozygous for allele T.

doi:10.1016/j.preghy.2011.08.085

P26. Increased inhibin A in severed preeclampsia/eclampsiaY. Arisanti, M.I.A. Akbar, B. Wicaksono, A. Sulistyono, E.G.Dachlan, M.D. Angsar (Obstetric and Gynecology Depart-ment, Airlangga University Medical Faculty, Dr. SoetomoHospital Surabaya, Indonesia)

Objectives: Inhibin is a glycoprotein hormone of aheterodimer made up of an a-subunit and one of twodistinct b-subunits, bA or bB that all three are produced bytropoblast cells where the function is to inhibit pituitaryFSH release.

Over this study we made assesment on maternal serumlevel of inhibin A, placental level and expression of inhibinA in severe pre-eclampsia.

284 Poster Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 1 (2011) 273–299