Lauritsen Marlene B, Nyegaard Mette, Betancur Catalina, Colineaux Catherine, Josiassen Trine L, Kruse Torben A, Leboyer Marion, Ewald Henrik
Department of Psychiatric Demography, Institute for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Risskov, Denmark.
Am J Med Genet B Neuropsychiatr Genet. 2003 Aug 15;121B(1):100-4. doi: 10.1002/ajmg.b.20050.
Infantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity. In the present study, we tested whether the alleles of twelve new single nucleotide polymorphisms (SNPs) in the SSTR5 gene were preferentially transmitted, using the transmission disequilibrium test (TDT) in a sample of 79 trios with autism (18 from Denmark and 61 from France). Furthermore, we combined four missense SNPs into haplotypes and searched for preferential transmission using the program TRANSMIT. No significant preferential transmission of the alleles and haplotypes of the twelve SNPs was found. Our results do not suggest the SSTR5 gene as a susceptibility gene for autism.
婴儿自闭症是一种具有很强遗传成分的广泛性发育障碍。其遗传模式似乎很复杂，尚未确定具体的易感基因。基于基因组扫描结果以及自闭症患者染色体异常的报告，16号染色体p13.3区域可能包含一个易感基因。生长抑素受体5（SSTR5）基因位于16号染色体p13.3区域，因此是自闭症的一个位置候选基因。SSTR5也可能是自闭症的一个功能候选基因，因为生长抑素可抑制生长激素分泌，并且在一些自闭症患者中已报道有生长激素反应增强的情况。此外，生长抑素能系统与多巴胺能系统相互作用，而多巴胺能系统被认为与自闭症的病因有关；特别是，生长抑素的分泌受多巴胺调节，多巴胺D2受体和SSTR5受体相互作用形成功能活性增强的受体复合物。在本研究中，我们在一个由79个自闭症三联体（18个来自丹麦，61个来自法国）组成的样本中，使用传递不平衡检验（TDT）来检测SSTR5基因中12个新的单核苷酸多态性（SNP）的等位基因是否存在优先传递情况。此外，我们将4个错义SNP组合成单倍型，并使用TRANSMIT程序搜索优先传递情况。未发现这12个SNP的等位基因和单倍型存在显著的优先传递情况。我们的结果并不表明SSTR5基因是自闭症的易感基因。
