Lack of Interaction between a Polymorphism in the Dopamine D2 Receptor Gene and the Clinical Features of Migraine

Abstract

The purpose of this study was to evaluate whether a particular genotype of the dopamine D2 receptor (DRD2) gene would affect the clinical features of migraine. In a group of 118 migraineurs (55 migraine with aura and 63 migraine without aura patients), we tested the association of the biallelic C/T NcoI DRD2 polymorphism with several characteristics of the disease. Genotype and allele frequencies resulted similarly distributed in migraine with aura and migraine without aura patients (chi2 = 1.58, P = 0.45 and chi2 = 0.09, P = 0.77, respectively). The different DRD2 genotypes (C/C, C/T and T/T) had no significant effects on age at onset of migraine, presence of premonitory phenomena, frequency of headache attacks, associated symptoms, psychological features and quality of life of our migraine patients. The results of our study do not support a role for the DRD2 gene in modifying the clinical features of migraine.

New genetic evidence for involvement of the dopamine system in migraine with aura

“…On the contrary, the possible association between MA and the D2 dopamine receptor gene (DRD2) SNP rs7131056 was not aYrmed by the enlargement of the control sample. Previous genetic studies had reported inconsistent results for several variants at the DRD2 locus (a silent change at amino acid position His313 of DRD2 named "NcoI polymorphism" (Dichgans et al 1998;Peroutka et al 1997Peroutka et al , 1998Rebaudengo et al 2004;Stochino et al 2003), with the underlying SNP meanwhile termed rs61689984; a (possibly functional) insertion/deletion polymorphism in the promotor region designated "-141C Ins/ Del" (Maude et al 2001); and an intronic dinucleotide repeat (Del Zompo et al 1998;Stochino et al 2003). None of these markers was included in the HapMap project and information on possible linkage disequilibrium (LD) between these previously genotyped polymorphisms and the haplotype-tagging SNPs tested in our study are not available.…”

“…Many migraine candidate genes have been analyzed in case-control or family based association studies during the past 10 years, among these several genes from the dopamine pathway (Asuni et al 2007;Cevoli et al 2006;de Sousa et al 2007;Del Zompo et al 1998;Dichgans et al 1998;Lea et al 2000;Maude et al 2001;Mochi et al 2003;Noble 2003;Peroutka et al 1997Peroutka et al , 1998Rebaudengo et al 2004;Shepherd et al 2002;Stochino et al 2003). However, most of the results of these association studies were negative, and positive Wndings could very often not be replicated.…”

“…However, most of the results of these association studies were negative, and positive Wndings could very often not be replicated. The dopamine D2 receptor gene is an illustrative case: several groups analyzed diVerent polymorphisms in this gene in patients with MA and/or MO, and signiWcant Wndings were reported in some of these studies for some of the genotyped polymorphisms (Del Zompo et al 1998;Peroutka et al 1997Peroutka et al , 1998), but could not be conWrmed by other groups (Dichgans et al 1998;Rebaudengo et al 2004;Stochino et al 2003). Diverse reasons may contribute to these inconsistencies: inadequate sample sizes, arbitrarily chosen polymorphisms, existence of diVerent risk alleles in diVerent populations, inadequate corrections for multiple testing, phenotypic diVerences between study populations (in which e.g., patients with MA, MO, childhood migraine, or any common type of migraine were included), and/or publication bias towards studies with positive results.…”

Migraine genetics and prospects for pharmacotherapy

“…Numerous studies have investigated genes involved in DA pathways. Certainly investigations of variants in the five DA receptor genes have provided conflicting results [Del Zompo et al, 1998;Dichgans et al, 1998;Maude et al, 2001;Mochi et al, 2003b;Peroutka et al, 1997;Rebaudengo et al, 2004] that require further clarification, but the most interesting results are evident in the DA b-hydroxylase (DBH) gene. Several functional polymorphisms have been reported for DBH, which encodes the enzyme playing an important role in regulating DA levels at the synapse.…”

Dopaminergic symptoms in migraine

“…In their genetic studies, Stochino et al [19,20] reported that the DRD2/NcoI C allele could be a susceptibility factor for good rizatriptan responsiveness, but did not confirm an association between dopaminergic genes and the migraine-panic phenotype. Using a family-based association method, others have reported that the allelic distribution at the DRD2 locus differs significantly in the dopaminergic migraineurs subgroup [21], although a more recent study argued against a role for the DRD2 gene in the migraine clinical phenotype [22]. Genetic variability in the DRD4 gene is involved in the predisposition to episodic migraine without aura, whereas susceptibility to chronic daily headache seems to involve genetic variability in the DAT gene [23,24].…”