中国北方汉族男性GDNF单核苷酸多态性与酒精依赖相关外表型的关联研究

Association between single nucleotide polymorphisms of the glial cell-derived neurotrophic factor gene and alcohol dependence related phenotypes in a northern Chinese Han population

目的:在中国北方汉族男性人群中,探讨GDNF基因rs3096140、rs3812047、rs11111与酒精依赖相关的焦虑、抑郁及攻击行为的关系。方法:在8家精神科专科医院招募326名符合DSM-IV酒精依赖诊断标准的汉族男性患者,292名健康对照,采用Buss-Perry攻击问卷评估攻击行为,ZUNG氏焦虑自评量表评估焦虑严重程度,ZUNG氏抑郁自评量表评估抑郁严重程度,采用TaqMan探针和连接酶检测反应进行SNP基因分型。结果:酒精依赖患者的攻击行为、焦虑和抑郁评分均高于健康对照(P <0. 001)。在酒精依赖患者中发现:rs11111 AG基因型患者的躯体攻击评分高于GG基因型患者(P <0. 01)。然而,在健康对照组中发现,rs3096140 CT基因型受试者的愤怒攻击评分高于CC基因型受试者(P <0. 01)。结论:酒依赖相关攻击行为和健康人的攻击行为存在不同的遗传机制,但均与GDNF基因的SNPs相关,不支持此三个SNPs与男性酒精依赖相关的焦虑、抑郁相关。

Objective: To investigate the relationship of single nucleotide polymorphisms( rs3096140,rs3812047 and rs11111) of glial cell-derived neurotrophic factor gene and alcohol dependence related phenotypes( depression,anxiety and aggression). Methods: Three hundred and twenty-six male alcohol dependence inpatients( according to DSM-IV diagnostic criteria) were recruited from 8 psychiatric hospitals in Northern China and292 normal controls were recruited from Northern China community. The Chinese version of the Buss-Perry Aggression Questionnaire( BPAQ) was used to measure aggressive behavior. The Self-Rating Anxiety Scale and Self-Rating Depression Scale was used to assess severity of anxiety and depression respectively. These three SNPs of GDNF genes were genotyped using the 5’ nuclease fluorescent TaqManTM primer. Results: The severity of aggressive behavior,anxiety and depression in alcohol dependent patients was higher than that of being in healthy controls( P <0. 001). The physical aggression scores were significantly higher in patients carrying rs11111 AG genotype than in patients with GG genotype( P < 0. 01). However,the anger aggression scores were significantly higher in normal subjects with rs3096140 CT genotype than in the healthy subjects with CC genotype( P < 0. 01). Conclusion:There are different genetic mechanisms for alcohol dependence related aggression and the aggression of healthy people,although all of them are related to the SNPs of the GDNF gene. No association between these three SNPs and alcohol dependence related anxiety or depression is found in a northern Chinese Han population.