5-HTTLPR genotype-specific phenotype in children and adolescents with autism
5-HTTLPR genotype-specific phenotype in children and adolescents with autism
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DOI：
10.1176/appi.ajp.163.12.2148
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发表时间：
2006-12-01
影响因子：
17.7
通讯作者：
Cook, Edwin H., Jr.
中科院分区：
文献类型：
--
作者：
Brune, Camille W.;Kim, Soo-Jeong;Cook, Edwin H., Jr.
目的：5-羟色胺转运体基因(SLC6A4)与焦虑、攻击性和注意力密切相关，且选择性5-羟色胺再摄取抑制剂(SSRIs)对某些行为症状有治疗作用，因此是自闭症的重要候选基因。在自闭症患者家庭中，目前存在SLC6A4的5-HTTLPR基因启动子多态(5-HTTLPR)两个等位基因(短、长)有偏向传递的报道。这些报告中的异质性可能是由于临床上的异质性。作者推测5-HTTLPR基因可能与自闭症儿童特定症状的变化有关。方法：探讨SLC6A4两个功能多态(5-HTTLPR，内含子2可变数串联重复序列[2 VNTR])变异是否与自闭症诊断访谈-修订版和自闭症诊断观察表的行为特征相关。结果：在修订后的自闭症诊断访谈中，发现了基因型-表型交互作用的证据，其中5-HTTLPR短型组(S/L或S/S)在亚域“未能使用非语言交流来调节社交”上被评为更严重，而长型组(L/L型)在亚域“刻板和重复的运动方式”和攻击性措施上被评为更严重。相比之下，在自闭症诊断观察表上，长时间组与定向面部表情和异常感官兴趣的严重程度有关。在修订的孤独症诊断访谈或孤独症诊断观察表中，内含子2 VNTR型与症状亚域之间没有显著的关系。结论：根据自闭症诊断访谈修订版和自闭症诊断观察表的评分，这些发现为自闭症患者5-HTTLPR的基因型特异性表型提供了初步支持。
Objective: The serotonin transporter gene (SLC6A4) is a strong autism candidate gene because of its association with anxiety, aggression and attention, and the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in treating certain behavioral symptoms. In families with individuals with autism, several reports of biased transmission of both alleles (short, long) at the serotonin transporter gene promotor polymorphism (5-HTTLPR) locus of SLC6A4 now exist. The heterogeneity in these reports may be due to clinical heterogeneity. The authors hypothesized that 5-HTTLPR genotypes would be related to variation in specific symptoms in children with autism.Method: The authors explored whether variants of two functional polymorphisms of SLC6A4 (5-HTTLPR, intron 2 variable number tandem repeat [ 2 VNTR]) were related to behavioral characteristics measured by the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Subjects (N = 73, age 3 -19 years old) met diagnostic criteria for autistic disorder based on both measures.Results: Evidence of genotype-phenotype interactions on the Autism Diagnostic Interview-Revised was found with the 5-HTTLPR short group of HTTLPR (S/ L or S/ S genotypes) being rated as more severe on the subdomain "failure to use nonverbal communication to regulate social interaction," and the long group (L/ L genotype) being more severe on the subdomain "stereotyped and repetitive motor mannerisms" and on an aggression measure. In contrast, on the Autism Diagnostic Observation Schedule, the long group was associated with greater severity on directed facial expressions and unusual sensory interests. There were no significant relationships between the intron 2 VNTR genotypes and subdomains or domains of symptoms on the Autism Diagnostic Interview-Revised or the Autism Diagnostic Observation Schedule. Conclusions: These findings provide initial support for genotype-specific phenotypes for 5-HTTLPR in autism based on ratings from the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule.