Ramoz Nicolas, Reichert Jennifer G, Corwin Thomas E, Smith Christopher J, Silverman Jeremy M, Hollander Eric, Buxbaum Joseph D
Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Biol Psychiatry. 2006 Jul 15;60(2):186-91. doi: 10.1016/j.biopsych.2006.01.009. Epub 2006 Apr 17.
The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function.
We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region.
No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results.
SLC6A4 variants do not appear to be significantly involved in the liability to autism.
长期以来，血清素转运体（5-HTT）被认为可能在自闭症中发挥作用。在一定比例的自闭症患者中一直发现有高血清素血症，并且使用选择性血清素再摄取抑制剂（SSRI）对治疗自闭症的某些症状可能有积极作用。已发现5-HTT基因SLC6A4的特定变体，尤其是插入缺失5-HTTLPR启动子位点，可调节其表达和转运体功能。
我们使用352个家庭的大型队列，研究了5-HTTLPR位点的短等位基因或长等位基因向受影响个体的传递。此外，我们筛选了先前报道与自闭症呈正相关的SLC6A4 5'区域中的五个单核苷酸多态性（SNP），以及同样在5'区域中的另外4个SNP。
未发现5-HTTLPR位点与自闭症有关联。此外，在我们的研究中，未观察到涵盖SLC6A4基因的九个SNP中的任何一个或其任何单倍型存在关联的证据。使用我们队列中的强迫行为（OCB）、严重OCB或刻板强迫性子集得出了相同的阴性结果。
SLC6A4变体似乎未显著参与自闭症易感性。
