Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene.

BACKGROUND/OBJECTIVES: Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21-q25, that encode different ADH isoforms. The ADH4 gene encodes the class II ADH4 pi subunit, which contributes, in addition to alcohol, to the metabolization of a wide variety of substrates, including retinol, other aliphatic alcohols, hydroxysteroids, and biogenic amines. The purpose of this study was to investigate the association of genetic variants within the ADH4 gene with cluster headache susceptibility and phenotype. METHODS: A total of 110 consecutive unrelated cluster headache patients and 203 age- and sex-matched healthy controls of Caucasian origin were involved in the study. Patients and controls were genotyped for 2 bi-allelic single nucleotide polymorphisms (SNPs) of the ADH4 gene: SNP1 - rs1800759 and SNP2 - rs1126671. Allele, genotype, and haplotype frequencies of the examined polymorphisms were compared between cases and controls. RESULTS: Genotype frequencies of the rs1126671 polymorphism resulted significantly different between cluster headache patients and controls (chi(2) = 10.269, P = .006). The carriage of the AA genotype, in comparison with remaining genotypes, was associated with a significantly increased disease risk (OR = 2.33, 95% CI: 1.25-4.37). Haplotype analysis confirmed the association between the ADH4 gene and the disease. No association between different clinical characteristics of cluster headache and the examined polymorphisms was found. CONCLUSION: Our data suggest that cluster headache is associated with the ADH4 gene or a linked locus. Additional studies are warranted to elucidate the role of this gene in the etiopathogenesis of the disease.

Increased plasma nitrites in migraine and cluster headache patients in interictal period: basal hyperactivity of L-arginine-NO pathway?

Nitrite concentrations in plasma were investigated in a population of migraine and cluster headache patients and a group of healthy non-headache controls. A hundred migraine patients and 69 cluster headache patients in the interictal period, and 112 controls, were studied. Significantly higher nitrite concentrations were found in migraine patients, with and without aura, and cluster headache patients, in remission and cluster phase, than in controls. These findings suggest that a basal dysfunction in the L-arginine-NO pathway may be involved in the peripheral mechanisms predisposing subjects with neurovascular headaches to individual attacks.

Kinetics and thermolability of platelet monoamine oxidase in cluster headache and migraine.

Platelet monoamine oxidase activity (MAO) from 33 cluster headache patients (17 males, 16 females) and 34 migraine patients (16 males, 18 females) was assayed. The kinetic constants (apparent Vmax and apparent Km) and the thermolability, measured as the ratio of the platelet MAO activity after and before heat treatment (+52 degrees C, 30 min), were determined. The MAO activity and Vmax values were significantly lower in cluster headache than in migraine and in both headache disorders compared to a control group (62 males, 66 females). When comparing all groups, Km was not significantly different except for migraine females, who had lower Km values compared to control females. Thermolability was significantly higher in cluster headache than in migraine and in both headache disorders compared to the control group. Smokers of five cigarettes or more per day had significantly lower Vmax values but similar Km and thermolability values compared to those smoking less or nothing. The findings of low maximal velocities and high thermolability of platelet MAO in cluster headache and migraine are suggested to represent constitutionally different enzyme properties.

Low platelet monoamine oxidase activity in headache: no correlation with phenolsulphotransferase, succinate dehydrogenase, platelet preparation method or smoking.

Platelet monoamine oxidase activity in male migrainous and cluster headache patients was significantly lower than in male controls, confirming our previous study. The activity range showed a normal distribution and low mean values could not be attributed to a subgroup with particularly low activity. When Corash 's platelet preparation method was used, with its high platelet yield, specific enzyme activities of a similar order were obtained. Thus, the low values encountered were not due to abnormal recovery within the platelet population. Two other enzyme activities, phenolsulphotransferase M and succinate dehydrogenase, were also measured in the same platelet samples. Although low succinate dehydrogenase activity was identified in the headache groups, it appeared to represent a separate phenomenon and there was no significant correlation between activity of either enzyme and that of monoamine oxidase. This shows that the low activity of platelet monoamine oxidase in headache is not related to a generalised platelet enzyme deficit. It was also shown that the low monoamine oxidase activity in the headache patients could not be attributed to smoking.

Pressor sensitivity to tyramine in patients with headache: relationship to platelet monoamine oxidase and to dietary provocation.

The pressor responses to oral and intravenous tyramine were not different from controls in migrainous patients with or without a history of attacks triggered by foods. However, patients who reported a dietary trigger were more likely to develop headache after tyramine administration than those without such a dietary history. Pressor responses to intravenous tyramine in patients with cluster headache were indistinguishable from controls. A group of five males with platelet monoamine oxidase activity one standard deviation or more below that of male controls required less intravenous tyramine to raise blood pressure by 30 mm Hg than males with monoamine oxidase levels within one standard deviation of the controls. This finding suggests that platelet monoamine oxidase activity to some extent reflects that of total body monoamine oxidase A plus B.

Platelet size: no correlation with migraine or monoamine oxidase activity.

A Coulter Model "S Plus" counter has been used to study platelets from 39 migrainous patients between attacks, six during attacks, eight with active cluster headache and 26 controls. None of the patient groups showed any abnormality in platelet size profile. There was no correlation between platelet monoamine oxidase activity and mean platelet volume in any of the groups.

Platelet monoamine oxidase activity and headache.

Mean platelet monoamine oxidase activity was reduced compared with control values in groups of headache-free male (but not female) patients suffering from classical migraine and from tension headache. Mean activity in male cluster patients, headache free, both during acute and quiescent phases of their illness, was also notably reduced. Retesting some migraine subjects after up to four years, showed that low activity may be a persistent feature: the correlation coefficient for repeated assays was 0.91 (p less than 0.01). There was no relationship between platelet monoamine oxidase activity and history of dietary migraine. A subgroup of headache patients with permanently low monoamine oxidase activity values may have been defined.

[Cytoenzymatic and cytoimmunological changes in capillary blood neutrophils of patients with Horton's headache]. / Zmiany cytoenzymatyczne i cytoimmunologiczne w neutrofilach krwi wlosniczkowej u chorych z bólem glowy Hortona.

In 11 patients with Horton's headache morphological investigations (differential white blood cell count), cytoenzymatic determinations (alkaline and acid phosphatase, non-specific esterase) and cytoimmunological tests (IgM and IgG binding) were carried out on capillary blood neutrophils obtained from the area of pain, non-painful area of the skin on the head on the contralateral side, and from the finger. The observed changes suggest an active participation of neutrophils in the pathological mechanism of Horton's headache and anaphylactoidal background of the disease.

Monoamine oxidase activities in patients with migraine or with cluster headache during the acute phases and after treatment with L-5-hydroxytryptophan.

The results of a study of the activity of platelet monoamine oxidase (MAO) in patients with migraine or with "Cluster headache" during the acute phases and after treatment with L-5-hydroxytryptophan are presented. MAO levels are higher in migraine subjects than in normals. There is, also, a clear difference between basal MAO levels in migraine sufferers and in Cluster Headache sufferers. The treatment with L-5-hydroxytryptophan tend to normalize MAO activity in the migraine patients, but does not change the MAO activity in cluster headache patients.