Background: Previous 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. 
Methods: In 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.
Results: Significant associations were observed for the rs1800497 genotype (χ ²=6.37, p =0.041) and allele (χ ²=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: χ ²=7.84, p =0.019; allele: χ ²=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: χ ²=6.88, p =0.032; allele: χ ²=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). 
Conclusion: Our 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.
Keywords: dopamine receptor D2, female, rs1800497, ELISA, migraine