title: Susceptibility to pre-eclampsia in Finnish women is associated with R485K polymorphism in the factor V gene, not with Leiden mutation.
abstract: This study determines whether genetic variability in the gene-encoding factor V contributes to differences in pre-eclampsia susceptibility. Allele and genotype frequencies of three single-nucleotide polymorphisms (SNPs) in the factor V gene leading to nonsynonymous changes (M385T in exon 8, and R485K and R506Q (Leiden mutation) in exon 10) were studied in 133 Caucasian women with pre-eclampsia and 112 healthy controls. Single-point analysis was expanded to haplotype analysis, and haplotype frequencies were estimated using an expectation-maximization algorithm. Comparison of single-point allele and genotype distributions of SNPs in exons 8 and 10 of the factor V gene revealed statistically significant differences in R485K allele (P=0.003) and genotype (P=0.03) frequencies between the patients and the control subjects. The A allele of SNP R485K was over-represented among the patients (12%) vs the control subjects (4%), at an odds ratio (OR) of 2.8 (95% confidence interval (CI) 1.2-6.2) for combined A genotypes (GA+AA vs GG). Allele and genotype differences between the patients and control subjects as regards M385T and Leiden mutation were not significant. In haplotype estimation analysis, there was a significantly elevated frequency of haplotype T-A-G encoding the M385-K485-R506 variant in the pre-eclamptic group vs the control group (P=0.01), at an OR of 2.6 (95% CI 1.2-5.5). We conclude that the T-A-G haplotype was more frequent among the patient group than in the control group, and genetic variations in the factor V gene other than the Leiden mutation may play a role in disease susceptibility.
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Fareeza
authors.initials: F
authors.lastname: Faisel
authors.forename: Eeva-Liisa
authors.initials: EL
authors.lastname: Romppanen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.forename: Jaana
authors.initials: J
authors.lastname: Laasanen
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Salonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
mesh_terms: D001120:Arginine / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy
chemical_list: C095381:factor V Leiden; D005165:Factor V; D001120:Arginine; D008239:Lysine