Association of expression of <em>DRD2 </em>rs1800497 polymorphism with migraine risk in Han Chinese individuals

Abstract

BackgroundPrevious studies suggested that single-nucleotide polymorphisms in dopamine receptor D2 (DRD2) are the susceptibility loci for migraine. This study was aimed at evaluating the contribution of DRD2 rs1800497 and its expression to migraine risk in Han Chinese subjects.MethodsIn total, 250 patients with migraine and 250 age- and sex-matched control subjects were included in this study. TaqMan allelic discrimination assay was used for DRD2 rs1800497 genotyping. Plasma DRD2 concentration was determined using enzyme-linked immunosorbent assay.ResultsSignificant associations were observed for the rs1800497 genotype (c2=6.37, p=0.041) and allele (c2=4.69, p=0.03; odds ratio [OR]=1.33, 95% CI=1.03–1.72, power=58%) frequencies between the migraine and control groups. Sex analysis indicated a positive association for rs1800497 between female patients with migraine and control individuals (genotype: c2=7.84, p=0.019; allele: c2=6.60, p=0.010; OR=1.61, 95% CI=1.12–2.30, power=73.4%). Furthermore, a significant association was observed only in female patients with migraine without aura (MO) (genotype: c2=6.88, p=0.032; allele: c2=5.65, p=0.017; OR=1.59, 95% CI=1.08–2.36, power=65.1%). The mean plasma DRD2 levels in the control group (mean±SD: 24.20±2.78) were significantly lower than those in the migraine with aura (MA) (30.86±3.69, p<0.0001) and MO groups (31.88±4.99, p<0.0001). Additionally, there was a sex-based difference in DRD2 expression in the MA (male vs female: 29.46±3.59 vs 32.27±3.27, p<0.01) and MO groups (male vs female: 29.18±3.50 vs 34.58±4.84, p<0.0001). Moreover, plasma DRD2 levels in patients were significantly different among the three genotypes (CC vs CT vs TT: 24.76±3.76 vs 30.93±3.85 vs 37.06±3.95, p<0.0001). Similar results were observed both in the MA (CC vs CT vs TT: 25.09±3.84 vs 28.57±2.84 vs 33.37±1.58, p<0.0001) and MO groups (CC vs CT vs TT: 24.65±3.79 vs 31.65±3.86 vs 38.29±3.74, p<0.0001).ConclusionOur case–control study suggested that the DRD2 polymorphism rs1800497 was significantly associated with the risk of migraine in Han Chinese females. Additionally, the plasma DRD2 level was high in patients with migraine. Females with migraine had considerably higher DRD2 levels than males with migraine. DRD2 expression may be regulated by DRD2 rs1800497 genotype in patients with migraine.

PACAP Induces Light Aversion in Mice by an Inheritable Mechanism Independent of CGRP

“…RNAs for other pituitary hormones (GH, TSH, prolactin) and receptors (GHRHR, Drd2) were also elevated only in responder males. The human dopamine receptor DRD2 gene was identified in a migraine association study (Deng et al, 2018b), and dopamine has long been implicated in migraine (Goadsby et al, 2017). Likewise, the elevated expression of prolactin is reminiscent of the role of prolactin and its receptor in sex-specific pain responses (Dussor et al, 2018;Patil et al, 2019).…”

Clinical implications of genetic polymorphisms in blepharospasm

“…Individuals with this mutation may have altered neuronal function, potentially affecting motor control ( 47 , 48 ). The SNP rs1800497 on chromosome 11q23.2 is located in exon 8 of the ankyrin repeat domain containing one gene downstream of DRD2( 49 ). Genetic variations in this receptor have been found to influence dopamine signaling, impacting motor function ( 50 ).…”

<p>Update on the pharmacogenomics of pain management</p>

“…This receptor is well-known as the site of action of many antipsychotic drugs, but it has also been studied in migraine headaches. A specific SNP rs1800497 was linked to increased prevalence of migraine headaches in Chinese females, leading to the proposal of the possible use of DRD2 antagonists in the prevention of treatment of migraine headaches 72…”