The hemochromatosis (HFE) gene influences the clinical features of migraine

Introduction Several studies suggested that iron metabolism may be involved in the pathogenesis of migraine. Iron concentrations in the periaqueductal gray matter of migraine patients are significantly increased. A large population-based study showed a high migraine prevalence in women with hemochromatosis (HH), a disease associated with progressive iron overload in several organs. The hemochromatosis gene (HFE) is located in 6p21.3 and encodes for a HLA class I-like molecule involved in iron metabolism. Two principal polymorphisms in the HFE gene, C282Y and H63D, have been identified as the cause of HH. Using a case-control design, we performed an association study in a cohort of Italian migraine patients to evaluate whether a particular allele or genotype of the HFE gene would modify the occurrence and the clinical features of the disease. Methods A total of 256 consecutive unrelated migraine patients (98 men, 158 women; mean age±SD=40.3±9.4 years) were involved in the study. The diagnosis of migraine was made according to the International Classification of Headache Disorders (ICHD-II) criteria. Two hundred and twenty-five patients fulfilled the diagnostic criteria for migraine without aura (MO) and 31 for migraine with aura (MA). A group of 237 sex-, age- and geographically (Northern Italy) matched healthy subjects (95 men, 142 women, mean age±SD=41.5±13.3 years) were used as controls. Patients and controls were genotyped for the C282Y and H63D polymorphisms of the HFE gene. Results Phenotype and allele frequencies of both polymorphisms were similarly distributed in migraine patients and controls. The patients carrying the DD genotype of the H63D polymorphism showed a later age at onset of the disease and an increased number of migraine attacks. Discussion Our data suggests that the HFE gene is not a major disease gene for migraine. However, the H63D polymorphism of the HFE gene may be considered a modifying genetic factor in migraine.