Migraine Genes and the Relation to Gender

Abstract

Migraine is an episodic brain disorder that is characterized by recurrent attacks of severe unilateral headache that are accompanied by various neurological symptoms. In addition, many patients have what is called an aura with visual and sensory disturbances. The majority of patients are female, suggesting that female hormones play an important role in the pathophysiology of the disorder. The molecular mechanisms, however, underlying this female preponderance are not well understood. It can be expected that the field of genetics that aims at identifying genetic factors that cause migraine by lowering the threshold for attacks will unravel some of these mechanisms. The 3 best known migraine genes encode ion transporters and were identified in families with familial hemiplegic migraine (FHM), a rare subtype of migraine with aura. FHM gene mutations cause alterations in mechanisms that control and modulate the neurotransmitter balance in the brain. Transgenic mice knock-in with human pathogenic mutations that were shown to exhibit some migraine-relevant features were very helpful in dissecting molecular mechanisms of migraine and pointed to a central role for cortical glutamate. In addition, transgenic mice that overexpress human RAMP1 exist and exhibit an increased sensitivity to calcitonin gene-related peptide. Findings from genetic and animal experiments on gender differences in migraine are discussed. Recently, a role for glutamate also came forward from a genome-wide association study in common migraine. By deciphering genetic and pathogenic migraine pathways, it can be expected that in the near future we will better understand mechanisms behind the female preponderance in migraine.

Abdominal Pain in Ulcerative Colitis

“…Female predominance and the importance of comorbid mood disorders have been repeatedly shown for pain syndromes, ranging from migraines to interstitial cystitis and functional gastrointestinal disorders 25, 31, 32 . Interestingly, both factors increased the risk of post-infectious IBS, thus linking inflammation as an inciting peripheral event with central facilitating or perpetuating factors, such as anxiety, catastrophizing and hypervigilance 26, 33 .…”

The risk of breast cancer associated with specific patterns of migraine history

“…Migraine with aura occurs more frequently at times in the menstrual cycle when estrogen levels are high. [6,17,7] Estrogen acts on the brain through several pathways,[11,18,19,10] increasing cortical and neuronal excitability,[20,21] and increasing the amplitude and rate of repetition of cortical spreading depression (CSD),[22] which is thought to cause, or be equivalent to, migraine with aura. [23-25,10] CSD is defined as alternating waves of neural excitation and suppression that spread across cortical tissue in the brain.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Migraine as a transient receptor potential channelopathy? The observation that more than half of patients have at least one first-degree relative with migraine implies a strong genetic predisposition (Shyti et al, 2011). Indeed, some rare familial forms of migraine are due to SNPs in genes encoding ion channels, including the Ca v 2.1 voltage-gated calcium channel, the Na v 1.1 voltage-gated sodium channel, and the TWIK-related spinal cord K + channel (TRESK) (reviewed in Van den Maagdenberg et al, 2010;Silberstein and Dodick, 2013).…”