Zwiya Hiba T, Samms-Vaughan Maureen, Bressler Jan, Lee MinJae, Byrd-Williams Courtney, Hessabi Manouchehr, Grove Megan L, Shakespeare-Pellington Sydonnie, Loveland Katherine A, Rahbar Mohammad H
Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Department of Child & Adolescent Health, The University of the West Indies (UWI), Mona Campus, Kingston, Kingston 7, Jamaica.
Res Autism Spectr Disord. 2023 Jul;105. doi: 10.1016/j.rasd.2023.102162. Epub 2023 Apr 28.
Male preponderance is well-established in children with autism spectrum disorder (ASD). Glutathione S-transferase (GST) genes play a crucial role in suppressing oxidative stress triggered by environmental stressors.
To determine whether the association between metals and ASD differs by sex and by GST genes.
Using data from 344 pairs of sex-and age-matched cases and controls, we assessed the association of each metal with ASD or ASD severity, by applying conditional logistic regression (CLR) or general linear models (GLM). Sex was assessed as an effect modifier in separate GST genetic models.
For Pb exposure, using a recessive model for the Ile105Val polymorphism, CLR revealed significant overall interaction between sex and ( = 0.04). However, sex-specific matched odds ratios revealed marginally lower odds of the Val/Val genotype among ASD cases than controls in females (MOR= 0.23 (95% CI): 0.05-1.11, = 0.06), but not among males (MOR= 1.18 (95% CI): 0.66-2.16, = 0.57) in the adjusted model. GLMs for Hg exposure detected significant overall interactions in co-dominant and recessive genetic models. For example, the mean difference in ASD severity among children with Val/Val genotype compared to those with Ile/Ile or Ile/Val were MOR= -0.26 and MOR= 1.30, respectively, in the adjusted model.
The association of Pb and Hg with ASD significantly differed by sex under the co-dominant and recessive genetic models. Such findings reflect potential sex differences in metal detoxification mechanisms. Replication is warranted due to the limited sample size of female participants.
在自闭症谱系障碍（ASD）儿童中，男性占比过高已得到充分证实。谷胱甘肽S -转移酶（GST）基因在抑制环境应激源引发的氧化应激中起关键作用。
确定金属与ASD之间的关联是否因性别和GST基因而异。
利用344对性别和年龄匹配的病例与对照的数据，我们通过应用条件逻辑回归（CLR）或一般线性模型（GLM）评估每种金属与ASD或ASD严重程度的关联。在单独的GST基因模型中，将性别作为效应修饰因素进行评估。
对于铅暴露，使用Ile105Val多态性的隐性模型，CLR显示性别与铅之间存在显著的总体交互作用（P = 0.04）。然而，性别特异性匹配优势比显示，在调整模型中，女性ASD病例中Val/Val基因型的优势比略低于对照组（MOR = 0.23（95%CI）：0.05 - 1.11，P = 0.06），但男性中并非如此（MOR = 1.18（95%CI）：0.66 - 2.16，P = 0.57）。汞暴露的GLM在共显性和隐性遗传模型中检测到显著的总体交互作用。例如，在调整模型中，与Ile/Ile或Ile/Val基因型儿童相比，Val/Val基因型儿童的ASD严重程度平均差异分别为MOR = -0.26和MOR = 1.30。
在共显性和隐性遗传模型下，铅和汞与ASD的关联因性别而异。这些发现反映了金属解毒机制中潜在的性别差异。由于女性参与者样本量有限，有必要进行重复研究。
