Kantojärvi Katri, Oikkonen Jaana, Kotala Ilona, Kallela Jenni, Vanhala Raija, Onkamo Päivi, Järvelä Irma
From the Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
Department of Biosciences, University of Helsinki, Helsinki, Finland.
Autism Res. 2015 Oct;8(5):634-9. doi: 10.1002/aur.1473. Epub 2015 Feb 23.
The arginine vasopressin receptor 1A gene (AVPR1A) is known to affect social communication and has been reported to associate with autism in several studies. Given that the microsatellite RS1 and a few SNPs in the promoter region of the AVPR1A have repeatedly associated with several traits, including autism it is rather surprising that the molecular explanation for these associations has remained unknown, although it has been reported that the allele length of the AVPR1A microsatellites might affect disease risk. Here we carried out an extended association analysis of three microsatellites and 12 tag single nucleotide polymorphisms (SNPs) in and around the AVPR1A gene in 205 Finnish families followed by promoter analysis. FBAT version v2.0.3 was used for family-based genetic association analyses of AVPR1A microsatellites and SNPs. The nearby microsatellite RS1 was found to harbor the best association. Interestingly, there are two potentially relevant transcription factor (TF) binding sites at RS1: for MEF2C and PBX, predicted with the Match algorithm in the TRANSFAC database. Sequence variations changing the affinity of these TFs might partly explain the AVPR1A promoter region associations shown in autism.
已知精氨酸加压素受体1A基因（AVPR1A）会影响社交沟通，并且在多项研究中已报道其与自闭症相关。鉴于AVPR1A启动子区域的微卫星RS1和一些单核苷酸多态性（SNP）多次与包括自闭症在内的多种性状相关，尽管有报道称AVPR1A微卫星的等位基因长度可能影响疾病风险，但这些关联的分子解释仍不清楚，这相当令人惊讶。在此，我们对205个芬兰家庭中AVPR1A基因及其周围的三个微卫星和12个标签单核苷酸多态性（SNP）进行了扩展关联分析，随后进行了启动子分析。使用FBAT v2.0.3版本对AVPR1A微卫星和SNP进行基于家系的遗传关联分析。发现附近的微卫星RS1具有最佳关联性。有趣的是，在RS1处有两个潜在相关的转录因子（TF）结合位点：分别为MEF2C和PBX的结合位点，通过TRANSFAC数据库中的Match算法预测得到。改变这些TF亲和力的序列变异可能部分解释了自闭症中显示的AVPR1A启动子区域关联。
