Brune Camille W, Kim Soo-Jeong, Hanna Gregory L, Courchesne Eric, Lord Catherine, Leventhal Bennett L, Cook Edwin H
Institute for Juvenile Research, Department of Psychiatry, University of Illinois-Chicago, Chicago, Illinois 60608, USA.
Autism Res. 2008 Apr;1(2):108-13. doi: 10.1002/aur.11.
Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons.
报告指出，神经元谷氨酸转运体基因SLC1A1（OMIM 133550，位于9号染色体p24）是强迫症（OCD）的一个定位和功能候选基因。自闭症中存在与强迫症相似的强迫观念和强迫行为，在自闭症谱系障碍（ASD）个体的全基因组连锁分析中发现了该区域，以及谷氨酸在ASD中的假定作用，使得SLC1A1也成为ASD的一个候选基因。为了测试SLC1A1与自闭症之间的关联，我们对86个严格定义的自闭症三联体中的三个先前与强迫症相关的单核苷酸多态性（SNP，rs301430、rs301979、rs301434）进行了基因分型。采用基于家系的关联测试（FBAT）的加性和隐性模型来检查关联。此外，还研究了为强迫症确定 的rs301430 - rs301979单倍型。FBAT显示，在隐性模型下，自闭症与一个SNP之间存在名义上显著的关联。rs301979的G等位基因向自闭症个体的传递不足（相当于在显性模型下C等位基因的过度传递）（Z = -2.47，P = 0.01）。在隐性模型下，G等位基因在T - G单倍型中也传递不足（Z = -2.41，P = 0.02）。在仅男性样本中也观察到了这两个结果。然而，它们在多重比较校正后不成立。
