Tochigi Mamoru, Kato Chieko, Koishi Shinko, Kawakubo Yuki, Yamamoto Kenji, Matsumoto Hideo, Hashimoto Ohiko, Kim Soo-Yung, Watanabe Keiichiro, Kano Yukiko, Nanba Eiji, Kato Nobumasa, Sasaki Tsukasa
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Department of Psychiatry, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
J Hum Genet. 2007;52(12):985-989. doi: 10.1007/s10038-007-0207-5. Epub 2007 Oct 24.
The gamma-aminobutyric acid (GABA) receptor genes GABRB3, GABRA5, and GABRG3 located on chromosome 15q11-q13 have been major candidates for susceptibility genes for autism, a neurodevelopmental disorder with a complex genetic etiology. In this study, we first investigated the association between the GABA receptor genes and autism in a Japanese population by analyzing 11 single nucleotide polymorphisms (SNPs). Intron 3 of GABRB3 was densely mapped because the previous studies observed the association of the microsatellite 155CA-2 located in the region. We observed no significant difference in allelic frequencies or genotypic distributions of the 11 SNPs between patients and controls. A permutation test showed no significant global differences in estimated haplotype frequencies between patients and controls. Analysis after confining the subjects to males showed similar results. Thus, this study provides no positive evidence of an association between the GABA receptor genes and autism in a Japanese population. However, in a SNP (rs3212337) located near the microsatellite 155CA-2, a significant deviation from the Hardy-Weinberg equilibrium was observed in patients (p = 0.029, corrected for multiple testing). This finding may suggest further studies around the markers for more definitive conclusions.
位于15号染色体q11 - q13区域的γ-氨基丁酸（GABA）受体基因GABRB3、GABRA5和GABRG3，一直是自闭症易感性基因的主要候选基因。自闭症是一种具有复杂遗传病因的神经发育障碍。在本研究中，我们首先通过分析11个单核苷酸多态性（SNP），调查了日本人群中GABA受体基因与自闭症之间的关联。对GABRB3的内含子3进行了密集定位，因为之前的研究观察到位于该区域的微卫星155CA - 2存在关联。我们发现患者和对照组之间这11个SNP的等位基因频率或基因型分布没有显著差异。置换检验表明患者和对照组之间估计的单倍型频率没有显著的总体差异。将研究对象限定为男性后的分析结果相似。因此，本研究没有提供日本人群中GABA受体基因与自闭症之间存在关联的阳性证据。然而，在靠近微卫星155CA - 2的一个SNP（rs3212337）中，观察到患者中存在显著偏离哈迪-温伯格平衡的情况（p = 0.029，经多重检验校正）。这一发现可能意味着需要围绕这些标记进行进一步研究以得出更明确的结论。
