Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Am J Med Genet B Neuropsychiatr Genet. 2009 Dec 5;150B(8):1147-51. doi: 10.1002/ajmg.b.30940.
In the present work, we provide further evidence for the involvement of the integrin alpha-4 precursor gene (ITGA4) in the etiology of autism, by replicating previous findings of a genetic association with autism in various independent populations. The ITGA4 gene maps to the autism linkage region on 2q31-33 and is therefore a plausible positional candidate. We tested eight single nucleotide polymorphisms (SNPs) in the ITGA4 gene region for association with autism in a sample of 164 nuclear families. Evidence for association was found for the rs155100 marker (P = 0.019) and for a number of specific marker haplotypes containing this SNP (0.00053 < P < 0.022). alpha4 integrins are known to play a key role in neuroinflammatory processes, which are hypothesized to contribute to autism. In this study, an association was found between the ITGA4 rs1449263 marker and levels of a serum autoantibody directed to brain tissue, which was previously shown to be significantly more frequent in autistic patients than in age-matched controls in our population. This result suggests that the ITGA4 gene could be involved in a neuroimmune process thought to occur in autistic patients and, together with previous findings, offers a new perspective on the role of integrins in the etiology of autism to which little attention has been paid so far.
在本研究中，我们通过在不同的独立群体中复制先前发现的与自闭症的遗传关联，为整合素 α4 前体基因（ITGA4）参与自闭症的发病机制提供了进一步的证据。ITGA4 基因定位于 2q31-33 的自闭症连锁区域，因此是一个合理的候选基因。我们在 164 个核心家庭样本中检测了 ITGA4 基因区域的 8 个单核苷酸多态性（SNP）与自闭症的关联。rs155100 标记物（P = 0.019）和包含该 SNP 的多个特定标记物单倍型与自闭症显著相关（0.00053 < P < 0.022）。α4 整合素已知在神经炎症过程中起关键作用，该过程被假设与自闭症有关。在这项研究中，我们发现 ITGA4 的 rs1449263 标记物与针对脑组织的血清自身抗体水平之间存在关联，在我们的人群中，与年龄匹配的对照组相比，自闭症患者的这种自身抗体明显更为常见。这一结果表明，ITGA4 基因可能参与了自闭症患者中发生的神经免疫过程，与先前的发现一起，为整合素在自闭症发病机制中的作用提供了一个新的视角，而这一作用迄今为止尚未得到足够的重视。
