title: -455G/A beta-fibrinogen gene polymorphism, factor V Leiden, prothrombin G20210A mutation and MTHFR C677T, and placental vascular complications.
abstract: Hyperfibrinogenaemia is associated with systemic arterial and venous thromboembolism and therefore may contribute to placental vascular disease associated with obstetric complications. The fibrinogen-raising -455G/A beta-fibrinogen gene polymorphism may enhance the physiological increase in fibrinogen levels during pregnancy and thereby predispose to obstetric complications. This retrospective case-control study looked at the association between the beta-fibrinogen gene polymorphism -455G/A, the hereditary thrombophilic markers factor V Leiden, prothrombin G20210A mutation (PGM) and C677T methylene tetrahydrofolate reductase (MTHFR), and obstetric complications associated with placental vascular disease. The study group (n = 247) comprised 147 women (90 Caucasian) who met the clinical criteria and a control group of 100 parous women (90 Caucasian) with no history of obstetric or medical complications. No significant differences were observed in the -455A allelic frequencies of the patient and normal control groups, with (allelic frequencies, 0.156 and 0.178, respectively; P = 0.5716, chi2 test, odds ratio = 1.17, 95% confidence interval = 0.65-2.13) or without (allelic frequencies, 0.129 and 0.170, respectively; P = 0.2077, chi2 test, odds ratio = 1.38, 95% confidence interval = 0.81-2.35) the exclusion of non-Caucasian women. There was an increased prevalence of factor V Leiden among Caucasian patients compared with normal controls (allelic frequencies, 0.056 and 0.017, respectively; P = 0.048, chi2 test, odds ratio = 0.29, 95% confidence interval = 0.05-1.15) but there were no differences in the prevalences of PGM or MTHFR. These data suggest that factor V Leiden is associated with an increased risk of obstetric complications, but that the -455A allele of beta-fibrinogen, PGM and MTHFR do not appear to be implicated.
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London School of Medicine, University College London Hospitals NHS Trust, London, UK. r.camilleri@ucl.ac.uk
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Camilleri
authors.forename: Donald
authors.initials: D
authors.lastname: Peebles
authors.forename: Carol
authors.initials: C
authors.lastname: Portmann
authors.forename: Tamara
authors.initials: T
authors.lastname: Everington
authors.forename: Hannah
authors.initials: H
authors.lastname: Cohen
mesh_terms: D020413:3' Untranslated Regions; D000037:Abruptio Placentae / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005317:Fetal Growth Retardation / Q000209:etiology; D005340:Fibrinogen / Q000032:analysis* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D021041:Placental Circulation / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000209:etiology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology*; D011250:Pregnancy Complications, Hematologic / Q000209:etiology*; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D005340:Fibrinogen; D042965:Methylenetetrahydrofolate Reductase (NADPH2)