一项人类白细胞抗原归因研究揭示了肠道炎症过程和自闭症谱系障碍之间的可能遗传相互作用
Laura Lombardi1,2,3, Sigrid Le Clerc2,3, Ching-Lien Wu1
1Université Paris Est Créteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie translationnelle, F-94010, Créteil, France.
Translational psychiatry
|July 5, 2023
概括
人类白细胞抗原 (HLA) 和丁类2 (BTNL2) 基因中的遗传变异与自闭症谱系障碍 (ASD) 风险有关. 这些发现表明,与ASD预防和治疗的潜在肠道相关途径.
科学领域:
- 免疫遗传学 免疫遗传学
- 神经发育障碍 神经发育障碍
- 人类遗传学 人类遗传学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种与免疫失调相关的神经发育状况.
- 人类白细胞抗原 (HLA) 和主要组织相容性复合体 (MHC) 基因与ASD风险有关,但研究不足.
- 炎症,自身免疫和失生症等免疫过程是ASD个体子组的关键.
研究的目的:
- 调查人类白细胞抗原 (HLA) 和主要组织相容性复合体 (MHC) 遗传变异与自闭症谱系障碍 (ASD) 风险的关联.
- 在这些区域内识别与ASD相关的特定单核酸多态 (SNPs) 和单核酸类型.
- 在ASD的背景下,探索BTNL2和HLA之间的潜在遗传相互作用.
主要方法:
- 使用了来自EU-AIMS联盟 (LEAP队列) 的全基因组关联研究 (GWAS).
- 对比HLA和MHC遗传变异,SNP和ASD个体的单元类型与典型的发展对照.
- 分析了六个重要的SNP (rs9268528, rs9268542, rs9268556, rs14004, rs9268557, rs8084) 和它们与ASD风险的关联.
主要成果:
- 六个SNP跨越了邦费罗尼值,确定了与ASD相关的三个独立的遗传块.
- 一个块 (rs9268528-G,rs9268542-G,rs9268556-C,rs14004-A) 提供了保护,而两个块 (rs9268557-T,rs8084-A) 增加了ASD风险.
- SNP rs8084和rs14004被映射到HLA-DRA,其他被映射到BTNL2,表明BTNL2和HLA之间存在遗传相互作用.
结论:
- 在HLA和BTNL2位点中的遗传变异与自闭症谱系障碍风险有显著的关联.
- 鉴定到的变异对基因表达和定量特征位置有影响,可能会影响肠道平衡和炎症.
- 这些发现表明,基因调节的肠道炎症过程与ASD风险之间存在联系,为预防和治疗提供了潜在的目标.
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