The common haemochromatosis mutation does not increase the risk of thrombosis in patients with factor V Leiden
A recent report suggested an association between heterozygosity for the common hereditary haemochromatosis mutation in the Hfe gene (C282Y) and the factor V Leiden mutation in patients with thrombosis (Xie et al, 1998). We have failed to find such an association in a similar study of a U.K. thrombophilic cohort.
Seventy-five unrelated subjects, all of whom were heterozygous for factor V Leiden and had a personal history of venous thrombosis, and 120 unrelated control subjects, 75 of whom were age and sex matched to the patients, were studied. Two control subjects were heterozygous for the factor V Leiden allele. DNA samples from all subjects were analysed for the presence of the G to A transition at nucleotide 845 of the Hfe gene that results in the C282Y substitution as previously described (Jouanolle et al, 1996). The frequency of C282Y carriership (defined as either heterozygosity or homozygosity for the mutation) was 20% (allele frequency 0.11, 95% CI 0.06–0.16) among the patients compared to 14.2% (allele frequency 0.08, 95% CI 0.05–0.11) in the control group, but this difference was not statistically significant (Table I).
Our results failed to show an association between factor V Leiden and the C282Y mutation and contrast with those of Xie et al (1998). This may reflect the different approaches used in the two studies to derive the frequency of C282Y carriership in the general population. Although our study selected control subjects from the same ethnic and geographic background as the patients, Xie et al (1998) based their approximate 6% prevalence in the Canadian population on the frequencies previously obtained in two control groups composed of Caucasian subjects of either Breton (carrier frequency 5.8%) or undisclosed (carrier frequency 6.4%) origin (Jouanolle et al, 1996; Feder et al, 1996). The prevalence of the C282Y mutation varies widely between populations. Thus, although the mutation is apparently absent from African, Asian and Australasian populations (Merryweather-Clarke et al, 1997), two studies in the U.K. and France found the frequency of C282Y carriership in the normal population to be 17% and 17.5% respectively (Willis et al, 1997; Jézéquel et al, 1998). Given these differences in geographic distribution of the C282Y mutation, we believe the approach adopted by Xie et al (1998) to approximate the prevalence of the C282Y mutation in their general population is inappropriate and that it is of critical importance when performing studies such as these to use a control population from the same geographic and ethnic background as the patients.
