ABSTRACT

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune functions. The aim of this study is to evaluate the relationship between cytokines IL6 and IL1B gene polymorphisms in ASD.

Methods: DNA isolations were performed in 95 children diagnosed with ASD and 84 unrelated healthy children, single-nucleotide changes in IL6 (rs1800796) and IL1B (rs1143634) genes were determined by using Real-Time PCR (Real-Time Polymerase Chain Reaction) method.

Results: IL6 rs1800796 polymorphism presented an elevated risk for the development of ASD with CG genotype and dominant model (CG+GG vs. CC), CG+GG carriers (OR = 1.867, p = 0.057; OR = 1.847, p = 0.055, respectively). CT genotype in IL1B rs1143634 polymorphism associated with 2.33 times elevated risk of autism and showed a significant association compared to wild-type CC genotype (p = 0.02). IL1B rs1143634 polymorphism presented a significantly elevated risk for the development of ASD with recessive model (CC+CT vs.TT), TT genotype (OR = 8.145, p = 0.02).

Conclusion: This study concludes that rs1143634 is associated with the risk of ASD in Turkish children. Determining these polymorphisms in a larger sample group may contribute to understanding the etiology of ASD and developing new treatment protocols.

Abbreviations: ASD: Autism spectrum disorder; DNA: Deoxyribonucleic acid; IL6: Interleukin 6; IL1B: Interleukin 1 beta; Real-time PCR: Real-time polymerase chain reaction; JAK-STAT: The Janus kinase/signal transducers and activators of transcription; MAPK: The mitogen-activated protein kinase; 5ʹUTR: The 5′ untranslated region; IL1α: Interleukin 1 alpha; IL-1Ra: Interleukin 1 receptor antagonist; NF-κB: Nuclear factor-kappa B; DSM-V: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; M-CHAT: Modified Checklist for Autism in Toddlers; EDTA: Ethylenediaminetetraacetic acid; gDNA: Genomic DNA; HWE: Hardy–Weinberg equilibrium; ANK2: Ankyrin 2; NL3: Neuroligin-3; XRCC4: X-ray repair cross complementing 4

摘要

背景：自闭症谱系障碍（ASD）是由遗传，环境和免疫因素引起的神经发育障碍。已知神经发育过程受免疫功能影响。这项研究的目的是评估ASD中细胞因子IL6和IL1B基因多态性之间的关系。

方法：对95例确诊为ASD的儿童和84例无关健康儿童进行DNA分离，采用实时PCR（实时聚合酶链反应）方法测定IL6（rs1800796）和IL1B（rs1143634）基因的单核苷酸变化。

结果： IL6 rs1800796多态性对具有CG基因型和优势模型（CG + GG vs. CC），CG + GG携带者（OR = 1.867，p = 0.057; OR = 1.847，p = 0.055，分别）。IL1B rs1143634基因多态性的CT基因型与自闭症风险增加2.33倍相关，并且与野生型CC基因型相比，具有显着相关性（p = 0.02）。IL1B rs1143634基因多态性与隐性模型（CC + CT vs.TT），TT基因型（OR = 8.145，p = 0.02）相比，提示ASD发生的风险显着升高。

结论：本研究得出的结论是，rs1143634与土耳其儿童发生ASD的风险有关。在较大的样本组中确定这些多态性可能有助于理解ASD的病因并开发新的治疗方案。

缩写： ASD：自闭症谱系障碍；DNA：脱氧核糖核酸；IL6：白介素6；IL1B：白介素1 beta；实时PCR：实时聚合酶链反应；JAK-STAT：Janus激酶/信号转导子和转录激活子；MAPK：有丝分裂原激活的蛋白激酶；5ʹUTR：5'非翻译区；IL1α：白介素1 alpha；IL-1Ra：白介素1受体拮抗剂；NF-κB：核因子κB；DSM-V：《精神疾病诊断和统计手册》第五版；M-CHAT：修改了自闭症幼儿的清单；EDTA：乙二胺四乙酸；乙二胺四乙酸。gDNA：基因组DNA；HWE：哈代-温伯格平衡；ANK2：锚蛋白2；NL3：Neuroligin-3；XRCC4：X射线修复交叉补充4