title: Factor V Leiden and thermolabile methylenetetrahydrofolate reductase gene variants in an East Anglian preeclampsia cohort.
abstract: Preeclampsia is a heritable condition that develops as a result of widespread vascular endothelial dysfunction. The thrombotic tendency in this condition has suggested a number of candidate genes, and there have been recent reports of positive association with the Leiden variant of factor V and the thermolabile variant of methylenetetrahydrofolate reductase. We attempted to reproduce these results in a large cohort of well-characterized women with preeclampsia, recruited prospectively within the East Anglian region of the United Kingdom. Women in the preeclampsia cohort (n=283) were genotyped for both the Leiden variant (G1691A) of factor V and the thermolabile variant (C677T) of methylenetetrahydrofolate reductase. Genotype and allele frequencies were compared with those of 2 control groups, one consisting of women recruited prospectively (n=100) from the same maternity hospital as the subjects and another consisting of normotensive women (n=100) from East Anglia. No significant differences were detected. Specifically, the carrier rate for the Leiden variant was 5.3% in the preeclampsia group and 5. 5% in the combined control group. T677 homozygotes for methylenetetrahydrofolate reductase were 11% and 11.5% in the 2 groups, respectively. We conclude that there is no evidence of association of preeclampsia with either of these 2 polymorphisms in our study population.
authors.affiliation: Clinical Pharmacology Unit, Department of Medicine, University of Cambridge Clinical School, Cambridge, UK. kmo22@medschl.cam.ac.uk
authors.forename: K M
authors.initials: KM
authors.lastname: O'Shaughnessy
authors.forename: B
authors.initials: B
authors.lastname: Fu
authors.forename: F
authors.initials: F
authors.lastname: Ferraro
authors.forename: I
authors.initials: I
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Downing
authors.forename: N H
authors.initials: NH
authors.lastname: Morris
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D004355:Drug Stability; D004739:England; D005165:Factor V / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012016:Reference Values; D015183:Restriction Mapping; D012307:Risk Factors; D013816:Thermodynamics
chemical_list: D017931:DNA Primers; C095381:factor V Leiden; D005165:Factor V; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)