去甲肾上腺素转运体、Gβ3基因多态性与双相障碍Ⅱ型的关联分析

Association of norepinephrine transporter and Gβ3 single nucleotide polymorphisms with bipolar disorder-Ⅱ

目的 通过去甲肾上腺素转运体（NET）相关第二信号转导通路部分中介分子的单核苷酸多态性（SNPs）与双相障碍关系的探讨,寻找双相障碍的生物学标记.方法 选择符合DSM-Ⅳ有关双相障碍-Ⅱ诊断标准、随访3年以上的患者152例（病例组）,健康对照187名（对照组）,采用连接酶检测反应（LDR）技术,测定NET基因的rs5569、rs2242446及Gβ3亚基基因的rs5433共3个SNPs进行检测,比较两组间3个SNPs的基因型及等位基因频度差异,采用最优尺度分析判断不同基因型与情感稳定剂疗效的关系.结果 病例组与对照组比较,3个位点的基因型及等位基因频度分布差异均无统计学意义（P〉0.05）;rs5433的TT型患者对情感稳定剂效果优于其他型,差异有统计学意义（P〈0.05）.结论 没有发现rs5569、rs2242446及rs5433与双相障碍的发病有关,但发现Gβ3基因多态性与情感稳定剂的预防复发效应有关,提示rs5433可能是使用情感稳定剂标志SNPs之一.

Objective To investigate the association of single nucleotide polymorphisms （SNPs） of intermediate molecules in the second signal transduction pathway of norepinephrine transporter （NET） with bipolar disorder,and look for biological markers of bipolar disorder.Methods Totals of 152 patients in accord with the diagnostic standard of bipolar disorder in DSM-Ⅳ who were followed for more than 3 years and 187 healthy controls were involved. Ligase detection reaction （LDR） was used to detect the genotypes of rs5569 and rs2242446 in NET,and rs5433 in Gβ3. The frequencies of genotypes and alleles were compared between two groups. Optimal scale analysis was used to determine the association between different genotypes and the effect of emotion stabilizer.Results No significant differences were found in frequencies of genotypes and alleles of three SNPs between two groups （P〉0.05）. Emotion stabilizer showed better effect on patients carried with TT genotype of rs5433 （P〈0.05）.Conclusions There are no association between SNPs rs5569,rs2242446 and rs5433 and bipolar disorder. The polymorphism of Gβ3 gene is related to recurrence prevention effect of emotion stabilizer, suggesting that rs5433 may be a marker SNP of emotion stabilizer.