Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients
Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients
复制标题
双相情感障碍患者多巴胺受体基因多态性与认知功能的关联研究
DOI：
10.1016/j.jad.2014.08.039
复制
发表时间：
2015
影响因子：
6.6
通讯作者：
Xiaohong Ma
中科院分区：
文献类型：
--
作者：
Liansheng Zhao;Yin Lin;Guohui Lao;Yingcheng Wang;Lijie Guan;Jinxue Wei;Zhenxing Yang;Peiyan Ni;Xuan Li;Zeyu Jiang;Li Tao;Xiaoyu Hao;Dongtao Lin;Liping Cao;Xiaohong Ma
目的探讨多巴胺受体基因多态性与双相情感障碍(BD)患者认知功能的相关性。方法采用Illumina GoldenGate基因分型技术，对375例双相情感障碍(BD-I)患者(病例组)和475例健康对照组(对照组)的23个单核苷酸多态(SNPs)进行基因分型。结果DRD4基因启动子区rs3758653的等位基因频率在患者组和对照组之间存在显著差异(χ2=9.386，校正后P=0.046)。有精神病性症状的BD-I患者与健康对照组比较，差异也有统计学意义(χ2=9.27，校正后P=0.049)。除TMTA错误和非法时间外，BD-I患者在所有认知领域的表现都显著低于健康对照组(P<；0.01)。在威斯康星卡片分类测验的非持久性错误(β=3.2，校正P=0.0034)中，DRD1rs5326基因的多态性与表型(受BD-I影响或未受BD-I影响)之间存在显著的交互作用。该等位基因对BD-I患者的WCST非持久性错误有正效应(β=2.8，校正后P=0.017)。基因关联分析也支持这一结果(F=4.24和P=0.007)，但在对照组中没有发现这种效应。限制样本量相对较小，单核苷酸多态性覆盖范围有限，得出结论时必须谨慎。结论DRD4基因可能在精神症状学中发挥重要作用，而不是在BD等单一诊断中发挥重要作用。DRD1基因与BD认知损害之间存在遗传关联。
ObjectiveTo determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD.MethodsTwenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education.ResultsThe allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ2=9.386, CorrectedP=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ2=9.27, CorrectedP=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (β=3.20 and CorrectedP=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (β=2.80 and CorrectedP=0.017). The genotypic association analyses also supported the findings (F=4.24 andP=0.007), but this effect was not found in controls.LimitationsThe sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion.ConclusionsDRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.