Werling Anna Maria, Bobrowski Elise, Taurines Regina, Gundelfinger Ronnie, Romanos Marcel, Grünblatt Edna, Walitza Susanne
University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
Department of Experimental Psychology, University of Regensburg, Regensburg, Germany.
J Neural Transm (Vienna). 2016 Mar;123(3):353-63. doi: 10.1007/s00702-015-1458-5. Epub 2015 Nov 11.
The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only. A case-control association study was performed for HFA (HFA, n = 105; controls, n = 133). Moreover, we performed a family-based association study (DFAM) analysis (HFA, n = 44; siblings, n = 57). Individuals were genotyped for the two most frequently reported single nucleotide polymorphisms (SNPs) in the CNTNAP2 gene (rs2710102, rs7794745). Furthermore, a meta-analysis using the MIX2 software integrated our results with previously published data. A significant association for the carriers of the T-allele of the rs7794745 with HFA was found in the case-control sample [OR = 1.547; (95 % CI 1.056-2.266); p = 0.025]. No association could be found by DFAM with any of the CNTNAP2 SNPs with HFA. The meta-analysis of both SNPs did not show a significant association with either ASD or with HFA. Overall, including case-control, sibs, and meta-analysis, we could not detect any significant association with the CNTNAP2 gene and HFA. Our results point in the direction that CNTNAP2 may not play a major role in HFA, but rather seems to have a significance in neurodevelopmental disorders or in individuals displaying intellectual delays.
接触蛋白相关蛋白样 2(CNTNAP2)基因已被讨论与自闭症谱系障碍(ASD)和其他神经发育障碍的不同症状相关。我们旨在阐明CNTNAP2在高功能自闭症(HFA)中的遗传关联,重点关注自闭症特异性症状并减少与智力相关的因素。此外,我们仅对ASD和HFA患者进行荟萃分析来比较我们的研究结果。对HFA进行了病例对照关联研究(HFA,n = 105;对照组,n = 133)。此外,我们进行了基于家系的关联研究(DFAM)分析(HFA,n = 44;兄弟姐妹,n = 57)。对CNTNAP2基因中两个最常报道的单核苷酸多态性(SNP)(rs2710102,rs7794745)进行个体基因分型。此外,使用MIX2软件进行的荟萃分析将我们的结果与先前发表的数据进行了整合。在病例对照样本中发现rs7794745的T等位基因携带者与HFA有显著关联[比值比(OR)= 1.547;(95%可信区间1.056 - 2.266);p = 0.025]。DFAM未发现任何CNTNAP2 SNP与HFA有关联。对这两个SNP的荟萃分析未显示与ASD或HFA有显著关联。总体而言,包括病例对照、同胞和荟萃分析,我们未检测到CNTNAP2基因与HFA有任何显著关联。我们的结果表明,CNTNAP2可能在HFA中不发挥主要作用,而似乎在神经发育障碍或表现出智力延迟的个体中具有重要意义。