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/ajp.2006.163.12.2148
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发表时间：
2006-12
期刊：
影响因子：
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通讯作者：
Camille W. Brune;Soo-Jeong Kim;Jeff Salt;B. Leventhal;C. Lord;E. Cook
中科院分区：
文献类型：
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作者：
Camille W. Brune;Soo-Jeong Kim;Jeff Salt;B. Leventhal;C. Lord;E. Cook
目的5-羟色胺转运体基因（SLC 6A 4）与焦虑、攻击性和注意力相关，并与选择性5-羟色胺再摄取抑制剂（SSRIs）治疗某些行为症状的有效性相关，因此被认为是自闭症的候选基因。在孤独症患者的家庭中，现在存在SLC 6A 4的5-HTTLPR基因启动子多态性（5-HTTLPR）位点的两个等位基因（短，长）的偏倚传递的几个报告。这些报告中的异质性可能是由于临床异质性所致。作者假设5-HTTLPR基因型与自闭症儿童特定症状的变化有关。方法探讨SLC 6A 4基因2个功能多态性（5-HTTLPR，intron 2 variable number tandem repeat [2 VNTR]）的变异体是否与自闭症诊断访谈修订版和自闭症诊断观察表测量的行为特征相关。受试者（N=73，年龄3-19岁）符合基于两种测量的自闭症障碍的诊断标准。结果：在自闭症诊断访谈-修订版中发现了基因型-表型相互作用的证据，HTTLPR的5-HTTLPR短组（S/L或S/S基因型）在子域“未能使用非语言交流来调节社会交往”上被评为更严重，而长组（L/L基因型）在子域“刻板和重复的运动习惯”和攻击性测量上更严重。相比之下，在自闭症诊断观察时间表上，长组与定向面部表情和不寻常的感官兴趣的严重程度相关。内含子2 VNTR基因型与自闭症诊断访谈修订版或自闭症诊断观察表上的症状子域或域之间没有显着关系。结论：这些研究结果提供了初步的支持，基因型特异性表型的5-HTTLPR在自闭症的基础上，从自闭症诊断访谈修订版和自闭症诊断观察时间表的评级。
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.