Choline acetyltransferase may contribute to the risk of Tourette syndrome: Combination of family-based analysis and case-control study
Choline acetyltransferase may contribute to the risk of Tourette syndrome: Combination of family-based analysis and case-control study
复制标题
胆碱乙酰转移酶可能会增加抽动秽语综合症的风险：基于家庭的分析和病例对照研究相结合
DOI：
10.1080/15622975.2017.1282176
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Li, Tang
中科院分区：
文献类型：
--
作者：
Yang, Xiuling;Liu, Wenmiao;Li, Tang
目的：双生子和家系分析表明Tourette综合征(TS)与遗传有关，尸检研究提出了TS患者胆碱能神经元减少的有趣可能性。方法：我们从中国汉族人群HapMap数据库中选择了胆碱乙酰转移酶(ChAT)的5个标签SNP(rs100824791、rs12264845、rs1880676、rs3793790和rs3793798)。对401例TS核心家系和405例对照进行了基因分型。结果：rs3793790存在显著的过度传递(TDT，(2)=9.121，P=0.003；HRR，(2)=6.579，P=0.01)，而病例对照分析显示，两组间无差异(基因型，(2)=0.436，P=0.804；等位基因，(2)=0.149，P=0.700)。Rs3793798与TS呈正相关(Tdt，(2)=5.025，P=0.028；HRR，(2)=0.250，P=0.617)。然而，在以家庭为基础的研究和病例对照研究中，其他三个被调查的SNP与TS无关。结论：我们的关联分析表明，Chat可能与中国汉族人TS易感性有关。这为胆碱能中间神经元参与TS的发病机制提供了有力的支持，并揭示了一个潜在的治疗靶点。
Objectives: Twin and family analyses have revealed a genetic contribution to Tourette syndrome (TS) and post-mortem studies have raised the intriguing possibility of a reduction in cholinergic interneuronsin TS patients.Methods: We selected five tag SNPs (rs100824791, rs12264845, rs1880676, rs3793790 and rs3793798) of choline acetyltransferase (CHAT) from the Han Chinese population Hapmap database. Genotyping was conducted on 401 TS nuclear family trios and 405 control subjects. Transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analyses were used to analyse the family-based study and a case-control study was also used to assess the genetic susceptibility to TS.Results: The results revealed a significant over-transmission of rs3793790 (TDT, (2)=9.121, P=0.003; HRR, (2)=6.579, P=0.01), while case-control analysis found no differences between the two groups (genotype, (2)=0.436, P=0.804; allele, (2)=0.149, P=0.700). Also, rs3793798 also indicated a positive association associated with TS (TDT, (2)=5.025, P=0.028; HRR, (2)=0.250, P=0.617). However, the other three SNPs investigated were found not to be associated with TS in both in the family-based and case-control studies.Conclusions: Our association analysis demonstrates that CHAT may contribute to TS susceptibility in the Han Chinese population. This gives strong support to the involvement of cholinergic interneurons in the aetiology of TS and reveals a potential therapeutic target.