Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT + TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF.

中文翻译：

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SNAP-25 单核苷酸多态性、边缘智力功能儿童的脑形态学和智力：中介分析。

边缘智力功能 (BIF) 是一种多因素疾病，其中遗传和环境因素都可能对临床结果产生影响。BIF 儿童的异常皮质发育和较低的 IQ 分数被证明是相关的，但这种情况的遗传成分及其与智力和大脑形态的可能联系从未在 BIF 中进行过研究。25 kD 的突触体相关蛋白 (SNAP-25) 参与突触可塑性、神经成熟和神经传递，影响智力功能。我们研究了 BIF 中的 SNAP-25 多态性，并将这种多态性与智力和皮层厚度相关联，使用社会经济地位和环境压力作为协变量作为决定智力能力的变量的良好代理。33 名诊断为 BIF 的儿童参加了这项研究。通过基因分型分析了SNAP-25多态性rs363050、rs363039、rs363043、rs3746544和rs1051312；通过 MRI 研究皮质厚度；使用 WISC-III/IV 分量表测量智力；在神经精神发育中发挥作用的环境压力因素被认为是协变量。结果表明，与携带 (CC) 基因型的儿童相比，携带以 (CT + TT) 基因型为代表的 rs363043(T) 次要等位基因的 BIF 儿童的特征是较低的感知推理指数和较低的全面智商得分 (p = 0.04) . 这种关联与左下顶叶皮层（直接效应 = 0.44）和左侧缘上回（直接效应 = 0.56）的厚度减少有关。