The objective of this study was to investigate the association between polymorphisms of the hypocretin receptor 2 gene (HCRTR2) and the risk of cluster headache (CH). The study is a meta-analysis of published case-control studies investigating the association between polymorphisms of the HCRTR2 gene and CH. Pooled odds ratios (OR) were estimated using both random (RE) and fixed effects (FE) models. Three studies, performed in five different European countries, with 593 cases and 599 controls, were included in the study. Allele G of the G1246A HCRTR2 polymorphism was significantly associated with CH (FE OR 1.58, CI 95% 1.27–1.95; RE OR 1.55 (1.14–2.12)). Carriers of the GG genotype showed a higher disease risk compared to the remaining genotypes (FE OR 1.75, CI 95% 1.37–2.25; RE OR 1.69, CI 95% 1.11–2.58). Our data confirm that the G1246A polymorphism of the HCRTR2 gene may modulate the genetic risk for CH.

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Several studies have suggested that iron metabolism may be involved in the pathogenesis of migraine. 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 haemochromatosis gene (HFE) would modify the occurrence and clinical features of the disease. We genotyped 256 migraine patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y and H63D polymorphisms of the HFE gene. 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. Our data suggest 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.