Summary
Several studies suggest that genetic factors may be involved in susceptibility to cluster headaches. Cluster headache patients often develop headache attacks after consuming alcohol. A recently published study from University of Torino in Italy examined possible links between alcohol and cluster headaches. According to the findings, there is a strong link between cluster headache and a gene called ADH4, which helps degrade alcohol in humans.

Purpose
“Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease.” It is known that alcohol can not only cause an attack of cluster headaches, but may also turn the episodic type of headache into a chronic and more distressing form.  The mechanism of this link between alcohol and cluster headaches has been unclear. Previously, some other types of headache, like migraines, have been linked to specific genes. The researchers hoped that they could find a link between cluster headaches and genes that were responsible for metabolizing alcohol in the body. Alcohol is degraded by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase (ADH). ADH is a protective enzyme that degrades alcohol without generating toxic by-products. A minimum of seven different genes encode this enzyme. The ADH4 gene has previously been linked to alcohol and drug dependence, so the researchers focused on this gene.

Methodology
•    110 male and female cluster headache patients were enrolled in this study. The patient group was compared to a control group of 203 people without headaches. Disorders related to alcohol use were also identified in both groups.
•    Blood was drawn from patients and normal individuals and these blood samples were used to test for presence of specific types of genes.
•    Genetic tests were performed to identify polymorphisms in the ADH4 gene in both the groups. The frequency of polymorphisms in the ADH4 gene was compared between them to find whether a specific gene occurred more often in patients of cluster headaches.

Key Findings
•    The ADH4 gene was found to be significantly associated with cluster headaches in this study.
•    Specifically, the occurrence of one particular genotype was markedly differently in cluster headache patients as compared to non-sufferers.
•    According to calculations based on the study findings, individuals who have a specific genotype (AA) of this gene have a more than two times greater risk of suffering from cluster headaches than those without this genotype.

Shortcomings
A link between ADH4 gene and cluster headaches seems likely. However, other genes that lie close to ADH4 may be the actual culprits. Also, genes and genetic mechanisms are very complex, which means that the ADH4 gene alone cannot explain the occurrence of cluster headaches. The authors in fact stress that although their findings show that the ADH4 gene may be a genetic risk factor for cluster headaches, more research is required to explore the mechanism of this link.

Conclusions
This study has shown that a real, not merely anecdotal, link does exist between alcohol use and cluster headaches. For patients suffering from cluster headaches, the results are a clear indicator to avoid alcohol use, particularly during the active phase of their disease. The study has provided a direction for further research to explore how genetic factors can make people susceptible to alcohol-induced cluster headaches In fact, the researchers have suggested that changes in the ADH enzyme may influence chemicals involved in the transmission of pain in the brain.

For More Information:
Cluster Headache Linked to Gene Responsible for Alcohol Metabolism
Publication Journal: Headache, January 2010
By Innocenzo Rainero MD, PhD, Elisa Rubino, MD; University of Torino, Italy

*FYI Living Lab Reports Are Summaries of the Original Research.