Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal, 700107, India.
Sci Rep. 2021 Mar 26;11(1):7010. doi: 10.1038/s41598-021-86496-5.
Alteration in gamma aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is speculated to be a potential risk factor for Autism Spectrum Disorder (ASD) due to an altered expression in the brain. Sensory, social, and emotional deficits of subjects with ASD were reported to be caused by an imbalance between excitatory and inhibitory neurotransmission as well as GABAergic dysfunction caused by inadequate receptor function. We for the first time studied association between ASD and a missense coding variant rs3810651 (I478F) in the GABRQ gene, encoding for one of the subunits of GABA receptors. Stratified analysis on families with ASD probands (N = 251) and ethnically matched control subjects (N = 250) revealed marginally higher frequency of "A" allele and "AA" genotype in female ASD probands as compared to gender matched controls. Female probands demonstrated higher severity for Verbal communication (χ = 5.75, P = 0.01), Activity level (χ = 7.26, P = 0.007), as well as Level and consistency of intellectual response (χ = 7.83 P = 0.005) in presence of "A/AA" warranting further in-depth investigation on the role of rs3810651 in ASD.
伽马氨基丁酸（GABA）的改变，主要的抑制性神经递质，由于大脑中的表达改变，被推测是自闭症谱系障碍（ASD）的潜在风险因素。据报道，ASD 患者的感觉、社交和情感缺陷是由于兴奋性和抑制性神经递质之间的不平衡以及由于受体功能不足导致的 GABA 能功能障碍引起的。我们首次研究了 GABRQ 基因中一个错义编码变异 rs3810651（I478F）与 ASD 之间的关联，该基因编码 GABA 受体的一个亚基。对 ASD 先证者（N=251）和种族匹配的对照（N=250）的家族进行分层分析显示，与性别匹配的对照相比，女性 ASD 先证者的"A"等位基因和"AA"基因型频率略高。女性先证者在存在"A/AA"时表现出更高的言语交流严重程度（χ=5.75，P=0.01）、活动水平（χ=7.26，P=0.007）以及智力反应的水平和一致性（χ=7.83，P=0.005），需要进一步深入研究 rs3810651 在 ASD 中的作用。
