Central Laboratory, Department of Clinical Laboratory, Affiliated Xiaoshan Hospital of Hangzhou Normal University, Hangzhou, 311202, Zhejiang, China.
Department of Clinical Laboratory, Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, 311202, Zhejiang, China.
Metab Brain Dis. 2021 Jun;36(5):865-870. doi: 10.1007/s11011-021-00699-3. Epub 2021 Mar 1.
Dysfunctions of the neurotransmitter system are related to the development of many psychological diseases including autism spectrum disorder (ASD). Single nucleotide polymorphisms (SNPs) are correlated with varied susceptibility of ASD and response to treatments. The association between SNPs in genes encoding serotonin and dopamine receptors and childhood ASD was examined in a Chinese Han population. Both autistic children (n = 319) and age-and gender-matched healthy controls (n = 347) were recruited from a local district. Disease severity was evaluated by the childhood autism rating scale (CARS). SNPs of rs6311 and rs6313 in the serotonin receptor HTR2A gene, rs4630328 in the dopamine receptor D2 (DRD2) gene and rs167771 in the DRD3 gene were examined. The CC genotype of rs6311 was significantly associated with an increased risk of ASD (odds ratio (OD) = 1.8 vs TT, 95% confidence interval (CI): 1.2-2.8, P = 0.0085). Carriers of the C allele of rs6311 had a significantly higher risk of childhood ASD (OD =1.3, 95% CI = 1.1-1.7, P = 0.0094). A strong linkage disequilibrium was observed between rs6311 and rs6313 (D' = 0.93, r = 0.86). There were significant correlations between haplotypes (T-A and C-G of rs6311-rs6313) and risk of childhood ASD. In contrast, the frequencies of genotypes and alleles of rs6313, rs4630328 and rs167771 were not significantly different between the case and control groups. All the SNPs examined were not associated with severity of the disease. Our study demonstrates that certain SNPs in the HTR2A gene, but not the DRD2 and DRD3, are associated with susceptibility to childhood ASD.
神经递质系统功能障碍与许多心理疾病的发展有关，包括自闭症谱系障碍（ASD）。单核苷酸多态性（SNP）与 ASD 的易感性和治疗反应有关。在汉族人群中，研究了编码 5-羟色胺和多巴胺受体的基因中的 SNP 与儿童 ASD 的关系。从当地一个区招募了自闭症儿童（n=319）和年龄和性别匹配的健康对照组（n=347）。使用儿童自闭症评定量表（CARS）评估疾病严重程度。研究了 5-羟色胺受体 HTR2A 基因中的 rs6311 和 rs6313、多巴胺受体 D2（DRD2）基因中的 rs4630328 和 DRD3 基因中的 rs167771 的 SNP。rs6311 的 CC 基因型与 ASD 风险增加显著相关（优势比（OR）=1.8 vs TT，95%置信区间（CI）：1.2-2.8，P=0.0085）。rs6311 的 C 等位基因携带者患儿童 ASD 的风险显著增加（OR=1.3，95%CI=1.1-1.7，P=0.0094）。rs6311 与 rs6313 之间存在强连锁不平衡（D'=0.93，r=0.86）。单体型（rs6311-rs6313 的 T-A 和 C-G）与儿童 ASD 风险之间存在显著相关性。相反，rs6313、rs4630328 和 rs167771 的基因型和等位基因频率在病例组和对照组之间无显著差异。研究中检查的所有 SNP 均与疾病严重程度无关。本研究表明，HTR2A 基因中的某些 SNP 与儿童 ASD 的易感性有关，但 DRD2 和 DRD3 基因中的 SNP 则不然。
