Evidence That HFE H63D Variant Is a Potential Disease Modifier in Cluster Headache

Cluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2022-02, Vol.72 (2), p.393-400
Main Authors: Papasavva, Maria, Vikelis, Michail, Katsarou, Martha-Spyridoula, Siokas, Vasileios, Dermitzakis, Emmanouil, Papademetriou, Christoforos, Karakostis, Konstantinos, Lazopoulos, George, Dardiotis, Efthimios, Drakoulis, Nikolaos
Format: Article
Language:English
Subjects:
Alleles
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cluster Headache - genetics
Clusters
Deoxyribonucleic acid
DNA
Frequency distribution
Genetic diversity
Genetic variance
Genotype
Headache
Headaches
Hemochromatosis
Hemochromatosis Protein - genetics
HFE protein
Histocompatibility Antigens Class I - genetics
Homeostasis
Homozygosity
Humans
Iron
Membrane Proteins - genetics
Metabolism
Migraine
Mutation
Neurochemistry
Neurology
Neurosciences
Patients
Phenotypes
Protein turnover
Proteomics
Subgroups
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Summary:Cluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have been associated with hereditary hemochromatosis (HH), an iron overload disorder. The objective of the current study was to examine the association of the more common HFE H63D variant, with the susceptibility to develop CH and diverse clinical phenotypes in a population of Southeastern European Caucasian (SEC) origin. Genomic DNA samples from 128 CH patients and 294 neurologically healthy controls were genotyped for the HFE rs1799945 (H63D) variant. H63D genotypic and allelic frequency distribution did not differ significantly between patients and controls ( p  > 0.05). Subgroup analysis revealed a significantly more frequent occurrence of the variant G allele in chronic compared to episodic CH patients, indicative for a possible correlation of the HFE gene with the susceptibility for disease chronification. Although homozygosity for the less prevalent H63D variant G allele was minimal in the CH cohort, the results of the present study are in accordance with previous studies in CH and migraine patients, suggesting that HFE H63D variant modifies the disease clinical characteristics. Hence, despite the absence of a per se association with CH susceptibility in the current SEC cohort, variability in HFE gene may be potentially regarded as a disease modifier genetic factor in CH.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-021-01913-8