title: Prevalence of HFE (hemochromatosis) gene mutations in patients with cluster headache.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurology III-Headache Center, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.forename: Chiara
authors.initials: C
authors.lastname: Rivoiro
authors.forename: Elisa
authors.initials: E
authors.lastname: Rubino
authors.forename: Valentina
authors.initials: V
authors.lastname: Milli
authors.forename: Walter
authors.initials: W
authors.lastname: Valfrè
authors.forename: Paola
authors.initials: P
authors.lastname: De Martino
authors.forename: Rossana
authors.initials: R
authors.lastname: Lo Giudice
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Angilella
authors.forename: Lidia
authors.initials: L
authors.lastname: Savi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pinessi
mesh_terms: D000328:Adult; D003027:Cluster Headache / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins