Almandil Noor B, Alismail Maram Adnan, Alsuwat Hind Saleh, AlSulaiman Abdulla, AbdulAzeez Sayed, Borgio J Francis
Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Front Med (Lausanne). 2023 Feb 1;10:1051039. doi: 10.3389/fmed.2023.1051039. eCollection 2023.
Autism Spectrum Disorder (ASD) is a multifactorial, neurodevelopmental disorder, characterized by deficits in communication, restricted and repetitive behaviors. ASD is highly heritable in Saudi Arabia; indecencies of affected individuals are increasing.
To identify the most significant genes and SNPs associated with the increased risk of ASD in Saudi females to give an insight for early diagnosis.
Pilot case-control study mostly emphasized on the significant SNPs and haplotypes contributing to Saudi females with ASD patients ( = 22) compared to controls ( = 51) without ASD. With the use of allelic association analysis tools, 243,345 SNPs were studied systematically and classified according to their significant association. The significant SNPs and their genes were selected for further investigation for mapping of ASD candidate causal variants and functional impact.
In females, five risk SNPs at ≤ 2.32 × 10 was identified in association with autism. The most significant exonic variants at chromosome 6p22.1 with olfactory receptor genes ( and ) clustered with high linkage disequilibrium through haplotyping analysis. Comparison between highly associated genes (56 genes) of male and female autistic patients with female autistic samples revealed that 39 genes are unique biomarkers for Saudi females with ASD.
Multiple variations in olfactory receptor genes ( and ) and single variations on and genes are contributing to ASD in females of Arab origin. Accumulation of these multiple predisposed coding SNPs can increase the possibility of developing ASD in Saudi females.
自闭症谱系障碍（ASD）是一种多因素神经发育障碍，其特征为沟通缺陷、受限及重复行为。ASD在沙特阿拉伯具有高度遗传性；受影响个体的发病率正在上升。
确定与沙特女性ASD风险增加相关的最重要基因和单核苷酸多态性（SNP），以便为早期诊断提供见解。
开展试点病例对照研究，主要关注与患有ASD的沙特女性患者（n = 22）相比，无ASD的对照（n = 51）中导致ASD的重要SNP和单倍型。使用等位基因关联分析工具，系统研究了243,345个SNP，并根据其显著关联进行分类。选择显著的SNP及其基因进行进一步研究，以绘制ASD候选因果变异图谱并分析其功能影响。
在女性中，鉴定出5个与自闭症相关的风险SNP，其P值≤2.32×10⁻⁶。通过单倍型分析发现，位于6p22.1染色体上与嗅觉受体基因（OR51E1和OR51E2）相关的最显著外显子变异以高连锁不平衡形式聚集。对男性和女性自闭症患者的高度相关基因（56个基因）与女性自闭症样本进行比较后发现，39个基因是沙特女性ASD的独特生物标志物。
嗅觉受体基因（OR51E1和OR51E2）的多个变异以及GRIN2B和SCN2A基因的单个变异导致了阿拉伯裔女性的ASD。这些多个易感编码SNP的积累会增加沙特女性患ASD的可能性。
