Deng Yingfeng, Huang Jianping, Zhang Huijun, Zhu Xueqin, Gong Qin
Department of Anesthesiology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.
J Pain Res. 2018 Apr 12;11:763-769. doi: 10.2147/JPR.S151350. eCollection 2018.
Previous studies suggested that single-nucleotide polymorphisms in dopamine receptor D2 () are the susceptibility loci for migraine. This study was aimed at evaluating the contribution of rs1800497 and its expression to migraine risk in Han Chinese subjects.
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 rs1800497 genotyping. Plasma DRD2 concentration was determined using enzyme-linked immunosorbent assay.
Significant associations were observed for the rs1800497 genotype (=6.37, =0.041) and allele (=4.69, =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: =7.84, =0.019; allele: =6.60, =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: =6.88, =0.032; allele: =5.65, =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, <0.0001) and MO groups (31.88±4.99, <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, <0.01) and MO groups (male vs female: 29.18±3.50 vs 34.58±4.84, <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, <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, <0.0001) and MO groups (CC vs CT vs TT: 24.65±3.79 vs 31.65±3.86 vs 38.29±3.74, <0.0001).
Our case-control study suggested that the 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 rs1800497 genotype in patients with migraine.
既往研究提示,多巴胺受体D2(DRD2)单核苷酸多态性是偏头痛的易感基因座。本研究旨在评估DRD2基因rs1800497多态性及其表达对汉族人群偏头痛风险的影响。
本研究共纳入250例偏头痛患者和250例年龄、性别匹配的对照者。采用TaqMan等位基因分型法对rs1800497进行基因分型。采用酶联免疫吸附测定法测定血浆DRD2浓度。
偏头痛组与对照组之间,rs1800497基因型(χ²=6.37,P=0.041)和等位基因(χ²=4.69,P=0.03;比值比[OR]=1.33,95%可信区间[CI]=1.03 - 1.72,检验效能=58%)频率存在显著关联。性别分析显示,女性偏头痛患者与对照个体之间rs1800497存在正相关(基因型:χ²=7.84,P=0.019;等位基因:χ²=6.60,P=0.010;OR=1.61,95%CI=1.12 - 2.30,检验效能=73.4%)。此外,仅在无先兆偏头痛(MO)女性患者中观察到显著关联(基因型:χ²=6.88,P=0.032;等位基因:χ²=5.65,P=0.017;OR=1.59,95%CI=1.08 - 2.36,检验效能=65.1%)。对照组血浆DRD2平均水平(均值±标准差:24.20±2.78)显著低于有先兆偏头痛(MA)组(30.86±3.69,P<0.0001)和MO组(31.88±4.99,P<0.0001)。此外,MA组(男性vs女性:29.46±3.59 vs 32.27±3.27,P<0.01)和MO组(男性vs女性:29.18±3.50 vs 34.58±4.84,P<0.0001)中DRD2表达存在性别差异。此外,患者血浆DRD2水平在三种基因型之间存在显著差异(CC vs CT vs TT:24.76±3.76 vs 30.93±3.85 vs 37.06±3.95,P<0.0001)。MA组(CC vs CT vs TT:25.09±3.84 vs 28.57±2.84 vs 33.37±1.58,P<0.0001)和MO组(CC vs CT vs TT:24.65±3.79 vs 31.65±3.86 vs 38.29±3.74,P<0.0001)也观察到类似结果。
我们的病例对照研究提示,DRD2基因多态性rs1800497与汉族女性偏头痛风险显著相关。此外,偏头痛患者血浆DRD2水平较高。女性偏头痛患者的DRD2水平显著高于男性偏头痛患者。偏头痛患者中,DRD2表达可能受rs1800497基因型调控。