Prevalence of HFE (hemochromatosis) gene mutations in patients with cluster headache.

Objective: To evaluate whether polymorphisms of the HFE gene would modify the occurrence and the clinical features of cluster headache (CH).

Background: Recent studies suggested that iron metabolism may be involved in the pathophysiology of primary headaches. The HFE gene encodes for a protein that modulates iron absorption. Mutations in this gene are responsible for toxic iron overload in several body organs.

Methods: Genomic DNA was extracted from 109 CH patients and 211 age and sex-matched healthy controls and genotyped for the C282Y and H63D mutations of the HFE gene. Allele and genotype frequencies of the HFE gene were compared between cases and controls. The clinical characteristics of the disease were compared according to the different HFE gene genotypes.

Results: No C282Y mutation was found in both cases and controls. The prevalence of the H63D mutation was nearly identical in cases and controls. The four patients carrying the HFE D63D genotype showed a significantly (P < .001) later age at onset of the disease in comparison with both H63H and H63D patients. The remaining clinical characteristics of the disease did not significantly differ in the presence or absence of the H63D mutation.

Conclusion: Our data do not support the hypothesis that genetic variations within the HFE gene are associated with CH. However, the HFE gene may influence the disease phenotype and may be regarded as a disease modifier gene.