Department of Biochemistry, University Institute of Biochemistry and Biotechnology, PMAS Arid Agriculture University, Rawalpindi 46000, Pakistan.
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Genes (Basel). 2020 Oct 15;11(10):1206. doi: 10.3390/genes11101206.
Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental and neuropsychiatric disorders in children characterized by impairment of communication and social interaction. Several genes with associated single nucleotide polymorphisms (SNPs) have been identified for ASD in different genetic association studies, meta-analyses, and genome-wide association studies (GWAS). However, associations between different SNPs and ASD vary from population to population. Four SNPs in genes , and SNP rs4307059 (which is found between and genes) have been identified and reported as candidate risk factors for ASD. The aim of the present study was, for the first time, to assess the association of SNPs in these genes with ASD in the Pakistani population. PCR-based genotyping was performed using allele-specific primers in 93 ASD and 93 control Pakistani individuals. All genetic associations, genotype frequencies, and allele frequencies were computed as odds' ratios (ORs) using logistic regression with a threshold of ≤ 0.01 to determine statistical significance. We found that the homozygous genotypes of mutant T alleles of and were significantly associated with Pakistani ASD patients in unadjusted ORs ( < 0.01), but their significance score was lost in the adjusted model. Other SNPs such as rs4307059, rs17850950 of , and rs1006737 of were not statistically significant. Based on this, we conclude that SNPs are not associated with, or are not the main cause of, autism in the Pakistani population, indicating the involvement of additional players, which need to be investigated in future studies in a large population size. One of the limitations of present study is its small sample size. However, this study, being the first on Pakistani ASD patients, may lay the foundations for future studies in larger samples.
自闭症谱系障碍（ASD）是一组复杂的多因素神经发育和神经精神障碍，以儿童沟通和社交互动障碍为特征。在不同的遗传关联研究、荟萃分析和全基因组关联研究（GWAS）中，已经确定了几个与 ASD 相关的具有关联单核苷酸多态性（SNP）的基因。然而，不同 SNP 与 ASD 之间的关联在不同人群中存在差异。在基因和 SNP rs4307059（位于和基因之间）中发现了四个 SNP，并被确定为 ASD 的候选风险因素。本研究的目的是首次评估这些基因中的 SNP 与巴基斯坦人群中 ASD 的关联。在 93 名 ASD 和 93 名对照巴基斯坦个体中，使用等位基因特异性引物进行基于 PCR 的基因分型。使用逻辑回归计算所有遗传关联、基因型频率和等位基因频率，以 odds' ratios (ORs) 表示，阈值为≤0.01，以确定统计学意义。我们发现，在未调整的 ORs 中（<0.01），和基因的突变 T 等位基因的纯合基因型与巴基斯坦 ASD 患者显著相关，但在调整后的模型中其显著性评分丧失。其他 SNP，如 rs4307059、的 rs17850950 和 rs1006737 ，则没有统计学意义。基于此，我们得出结论，SNP 与巴基斯坦人群中的自闭症无关，或者不是自闭症的主要原因，表明还存在其他因素，需要在未来的大规模人群研究中进行调查。本研究的一个局限性是样本量小。然而，作为对巴基斯坦 ASD 患者的首次研究，本研究可能为未来在更大样本量中进行的研究奠定基础。
