Clemens Tempfer

Polymorphisms of Thrombophilic and Vasoactive Genes and Severe Preeclampsia: A Pilot Study

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 solidphase 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, angiotensiongen (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.

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage

OBJECTIVEnTo investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy.nnnDESIGNnProspective case control study.nnnSETTINGnAcademic research institution.nnnPATIENT(S)nOne hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss.nnnINTERVENTION(S)nPeripheral venous puncture.nnnMAIN OUTCOME MEASURE(S)nPolymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles.nnnRESULT(S)nNo association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed.nnnCONCLUSION(S)nThis is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Low-Grade Myxofibrosarcoma of the Vulva in a 15-Year-Old Adolescent A Case Report

Myxofibrosarcoma is a rare tumor in adolescence, which was originally described as the myxoid variant of malignant fibrous histiocytoma (MFH) [1]. This entity consists of several histologic subtypes and the histopathological examination is the gold standard in establishing the definitive diagnosis. Once the diagnosis has been established, complete tumor resection is the mainstay of treatment to minimize the risk of local recurrence [2]. A 15-year-old girl was admitted to our hospital in November 2002 with a history of cachexia due to extensive weight loss and intermittent collapses over the past few months. On admission, physical examination revealed an actual weight of 42 kilograms (third percentile) and a striking pale skin, but no further abnormalities. The blood count showed leucocytosis (25,000/pL) and anaemia with a hemoglobin count of 6.7 g/dL. Examination of external genital revealed a large tumor of the vulva with a size of about 20 cm in di-

Body Mass Index but Not a Polymorphism of the Interleukin-1 Receptor Antagonist (IL-1 RA) Gene Is Associated with Age at Natural Menopause

Background: A genetic component of the onset of menopause has been described and several candidate genes have been identified. We hypothesized that carriage of a polymorphism of the interleukin-1 receptor antagonist gene (IL-1 RA) is associated with an early age at menopause. Methods: In a prospective cohort study, 90 consecutive postmenopausal Caucasian women were genotyped by PCR for the presence of an 86-base pair tandem repeat polymorphism in intron 2 of IL-1 RA. Results: We found that 36/90 (40%) women were homozygous for the wild-type allele 1 and 49/90 (54%) women were heterozygous for any of the variant alleles (1/2 [n = 44], 1/3 [n = 3], 2/3 [n = 2]). Two women (2%) were homozygous carriers of the variant allele 2. The wild-type allele 1 was identified on 119 of 180 chromosomes for an allele frequency of 0.66. The polymorphic alleles 2 and 3 were present on 56 and 5 chromosomes, respectively (allele frequencies 0.31 and 0.03, respectively). No correlation between the IL-1 RA genotype and the age at menarche and menopause, the length of the reproductive period, and the number of deliveries and miscarriages was ascertained. As to allele frequencies, homozygous and heterozygous carriers of the variant allele 2 had a median age at menopause of 50 (range 40–48) years, compared to 49.5 (range 39–56) years for women with no allele 2 (p value 0.41). Women with at least one allele 2 had a median age at menarche of 13 (range 10–16) years, compared to 13 (range 10–17) years for women with no allele 2 (p value 0.1). Decreasing body mass index, but not smoking, was correlated with an increasing age at natural menopause (r = –0.23, p = 0.04). Conclusions: Our preliminary data suggest that an 86-base pair tandem repeat polymorphism in intron 2 of IL-1 RA does not modulate the onset and cessation of menses in this cohort of Caucasian women.