Headache and Genetics

Abstract

Migraine is considered as a complex polygenic disease in which the

genetic factors interact with the environmental factors. There is a variety

of evidence emphasizing that genetic factors take more role in migraine

with aura than migraine without aura. Responsible loci, predisposition

genes and their number remain to be unknown.

The autozomal dominantly inherited monogenic migraine form, which is

called as familial hemiplegic migraine, is now proved to be definitely

caused by mutations in the genes related to the calcium channel

(CACNA1A), Na-K-ATPase pump (ATP1A2) and the sodium channel

(SCN1A). These data support the idea that migraine is a channelopathy,

that is, an ion channel disease. Another interesting dimension of this

phenomenon is that migraine without aura or totally normal phenotype

can be found in some family members who inherit these mutations.

On the other hand, two of these genes -that were discovered first- were

investigated and found to form no significant predisposition region for

the other common migraine phenotypes except for a few cases.

Interestingly, in several trials, it has been determined that a locus in the

19p13 region, telomeric neighbor of this gene, has an association with

the predisposition for migraine with aura; however this region is

different from CACNA1A. The linkage analysis studies have shown

distinct linkage regions on quite different chromosomes; the results of

some studies has not been verified by others due to the methodological

reasons and more importantly for the ethnical diversities. Numerous

studies that investigate the association of the genes –that can be

considered as candidates- with polymorphism are available, but their

significance is not yet clear.

The fact that in the future migraine genetics research will clarify the genes

of common and serious forms is important in terms of specific diagnosis

and treatment. It is important that migraine, which is considered by the

World Health Organization not only as one of the most serious causes of

disability but also as a personal and social problem, is investigated by each

society with regard to its own genetic factors due to the intersociety

d i f f e r e n c e s