Susceptibility to pre-eclampsia in Finnish women is associated with R485K polymorphism in the factor V gene, not with Leiden mutation.

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.