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Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study.
J Soc Gynecol Investig. 2004 May; 11(4):227-31.JS

Abstract

OBJECTIVE

Carriage of thrombophilic and vasoactive polymorphic alleles has been associated with various pregnancy complications. The effect of carrying multiple polymorphisms is not known. We conducted a case-control study to determine the association between eight polymorphisms of thrombophilic and vasoactive genes and the risk of severe preeclampsia.

METHODS

The following polymorphisms were analyzed by sequencing-on-chip-technology using solid-phase polymerase chain reaction on oligonucleotide microarrays: factor 5 (F5) Leiden, factor 2 (F2)-prothrombin G20210A, plasminogen activator inhibitor (PAI)-1 4G/5G, nitric oxide synthase (NOS) 3 T768C, NOS 3 Glu298Asp, angiotensinogen (AGT) Met235Thr, estrogen receptor (ER) alpha Pvu II, and mineralcorticoid receptor (MLR) Ser810Leu. The study comprised 24 patients with severe preeclampsia and 24 controls from a cohort of consecutive white women treated at the Obstetrics Department of the University of Vienna Medical School. Genotypes were correlated with clinical data.

RESULTS

The investigated polymorphisms did not influence the risk of severe preeclampsia independently. When separately considering the simultaneous carriage of multiple thrombophilic or vasoactive polymorphisms, neither the combined carriage of thrombophilic polymorphisms (F5 Leiden, F2 G20210A, PAI-1 4G/5G), nor the combined carriage of vasoactive polymorphisms (NOS 3 T768C, NOS 3 Glu298Asp, AGT Met235Thr) conferred an increased risk of severe preeclampsia. Cumulative genotype frequencies for at least two homozygous mutant genotypes, however, were nine of 24 (38%) and two of 24 (8%) for the study and control groups, respectively (P <.05). All of these nine women with severe preeclampsia had at least two homozygous mutant genotypes of four polymorphisms, ie, F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, or ER alpha Pvu II.

CONCLUSION

Our data fail to document an independent significant influence of the investigated polymorphisms on the risk of severe preeclampsia. In an attempt to build a multigenetic model of severe preeclampsia, the combination of F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, and ER alpha Pvu II was the most effective combination to predict the presence of severe preeclampsia in this small series of white women.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Albert-Ludwig University Medical School, Freiburg, Germany. tempfer@frk.ukl.uni-freiburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15120696

Citation

Tempfer, Clemens B., et al. "Polymorphisms of Thrombophilic and Vasoactive Genes and Severe Preeclampsia: a Pilot Study." Journal of the Society for Gynecologic Investigation, vol. 11, no. 4, 2004, pp. 227-31.
Tempfer CB, Jirecek S, Riener EK, et al. Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study. J Soc Gynecol Investig. 2004;11(4):227-31.
Tempfer, C. B., Jirecek, S., Riener, E. K., Zeisler, H., Denschlag, D., Hefler, L., & Husslein, P. W. (2004). Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study. Journal of the Society for Gynecologic Investigation, 11(4), 227-31.
Tempfer CB, et al. Polymorphisms of Thrombophilic and Vasoactive Genes and Severe Preeclampsia: a Pilot Study. J Soc Gynecol Investig. 2004;11(4):227-31. PubMed PMID: 15120696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study. AU - Tempfer,Clemens B, AU - Jirecek,Stefan, AU - Riener,Eva-Katrin, AU - Zeisler,Harald, AU - Denschlag,Dominik, AU - Hefler,Lukas, AU - Husslein,Peter W, PY - 2004/5/4/pubmed PY - 2004/12/16/medline PY - 2004/5/4/entrez SP - 227 EP - 31 JF - Journal of the Society for Gynecologic Investigation JO - J Soc Gynecol Investig VL - 11 IS - 4 N2 - OBJECTIVE: Carriage of thrombophilic and vasoactive polymorphic alleles has been associated with various pregnancy complications. The effect of carrying multiple polymorphisms is not known. We conducted a case-control study to determine the association between eight polymorphisms of thrombophilic and vasoactive genes and the risk of severe preeclampsia. METHODS: The following polymorphisms were analyzed by sequencing-on-chip-technology using solid-phase polymerase chain reaction on oligonucleotide microarrays: factor 5 (F5) Leiden, factor 2 (F2)-prothrombin G20210A, plasminogen activator inhibitor (PAI)-1 4G/5G, nitric oxide synthase (NOS) 3 T768C, NOS 3 Glu298Asp, angiotensinogen (AGT) Met235Thr, estrogen receptor (ER) alpha Pvu II, and mineralcorticoid receptor (MLR) Ser810Leu. The study comprised 24 patients with severe preeclampsia and 24 controls from a cohort of consecutive white women treated at the Obstetrics Department of the University of Vienna Medical School. Genotypes were correlated with clinical data. RESULTS: The investigated polymorphisms did not influence the risk of severe preeclampsia independently. When separately considering the simultaneous carriage of multiple thrombophilic or vasoactive polymorphisms, neither the combined carriage of thrombophilic polymorphisms (F5 Leiden, F2 G20210A, PAI-1 4G/5G), nor the combined carriage of vasoactive polymorphisms (NOS 3 T768C, NOS 3 Glu298Asp, AGT Met235Thr) conferred an increased risk of severe preeclampsia. Cumulative genotype frequencies for at least two homozygous mutant genotypes, however, were nine of 24 (38%) and two of 24 (8%) for the study and control groups, respectively (P <.05). All of these nine women with severe preeclampsia had at least two homozygous mutant genotypes of four polymorphisms, ie, F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, or ER alpha Pvu II. CONCLUSION: Our data fail to document an independent significant influence of the investigated polymorphisms on the risk of severe preeclampsia. In an attempt to build a multigenetic model of severe preeclampsia, the combination of F5 Leiden, NOS 3 T768C, NOS 3 Glu298Asp, and ER alpha Pvu II was the most effective combination to predict the presence of severe preeclampsia in this small series of white women. SN - 1071-5576 UR - https://www.unboundmedicine.com/medline/citation/15120696/Polymorphisms_of_thrombophilic_and_vasoactive_genes_and_severe_preeclampsia:_a_pilot_study_ L2 - https://www.diseaseinfosearch.org/result/5920 DB - PRIME DP - Unbound Medicine ER -