Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
Mol Autism. 2012 Jun 9;3(1):4. doi: 10.1186/2040-2392-3-4.
A growing number of clinical and basic research studies have implicated immunological abnormalities as being associated with and potentially responsible for the cognitive and behavioral deficits seen in autism spectrum disorder (ASD) children. Here we test the hypothesis that immune-related gene loci are associated with ASD.
We identified 2,012 genes of known immune-function via Ingenuity Pathway Analysis. Family-based tests of association were computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository. Several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, we observed significant associations in the CD99 molecule-like 2 region (CD99L2, rs11796490, P = 4.01 × 10-06, OR = 0.68 (0.58-0.80)), in the jumonji AT rich interactive domain 2 (JARID2) gene (rs13193457, P = 2.71 × 10-06, OR = 0.61 (0.49-0.75)), and in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 × 10-06, OR = 1.46 (1.24-1.72)).
This study suggests that despite the lack of a general enrichment of SNPs in immune function genes in ASD children, several novel genes with known immune functions are associated with ASD.
越来越多的临床和基础研究表明，免疫异常与自闭症谱系障碍（ASD）儿童的认知和行为缺陷有关，并可能是其致病原因。在此，我们检验了免疫相关基因座与 ASD 相关的假说。
通过 Ingenuity 通路分析，我们确定了 2012 个具有已知免疫功能的基因。在自闭症基因资源交换（AGRE）数据库中，对来自 2012 个免疫相关基因的 22904 个单核苷酸多态性（SNP），在可用的 1510 个三核苷酸重复序列中进行了基于家系的关联测试。在调整了多次比较后，一些免疫相关基因中的 SNPs 仍与 ASD 具有统计学显著相关性。具体来说，我们在 CD99 分子样 2 区（CD99L2，rs11796490，P=4.01×10-06，OR=0.68（0.58-0.80））、 jumonji AT 富含区 2 基因（JARID2，rs13193457，P=2.71×10-06，OR=0.61（0.49-0.75））和甲状腺过氧化物酶基因（TPO，rs1514687，P=5.72×10-06，OR=1.46（1.24-1.72））中观察到了显著的相关性。
本研究表明，尽管 ASD 儿童中免疫功能基因的 SNP 普遍缺乏富集，但具有已知免疫功能的几个新基因与 ASD 相关。
