Functional Genomics, Centre for Neurogenomics and Cognitive Research, VU Medical Center and VU University, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands.
Genes Brain Behav. 2012 Oct;11(7):767-71. doi: 10.1111/j.1601-183X.2012.00819.x. Epub 2012 Jul 28.
Intellectual disability (ID) is an unresolved health care problem with a worldwide prevalence rate of 2-3%. For many years, research into the genetic causes of ID and related disorders has mainly focused on chromosomal abnormalities or X-linked genetic deficits. Only a handful of autosomal genes are known to cause ID. At the same time it has been suggested that at least some cases of ID represent an extreme form of normal intellectual ability and therefore that genes important for intellectual ability in the normal range may also play a role in ID. In this study, we tested whether the autosomal SNAP25 gene, which was previously associated with variation in intellectual ability in the normal range, is also associated with ID. The gene product of SNAP25 is an important presynaptic plasma membrane protein, is known to be involved in regulating neurotransmitter release, and has been linked to memory and learning by its effect on long term potentiation in the hippocampus. Allele frequencies of two genetic variants in SNAP25 previously associated with intellectual ability were compared between a group of 636 ID cases (IQ < 70) and a control group of 361 persons of higher than average intellectual ability. We observed a higher frequency of the putative risk allele of rs363050 (P = 0.02; OR = 1.24) in cases as compared to controls. These results are consistent with a role of SNAP25 in ID, and also support the notion that ID reflects the lower extreme of the quantitative distribution of intellectual ability.
智力残疾（ID）是一个全球性的健康问题，其患病率为 2-3%。多年来，对 ID 及相关障碍的遗传原因的研究主要集中在染色体异常或 X 连锁的遗传缺陷上。只有少数常染色体基因被认为会导致 ID。同时，有人认为，至少有一些 ID 病例代表了正常智力能力的极端形式，因此，对正常范围内智力能力重要的基因也可能在 ID 中发挥作用。在这项研究中，我们测试了常染色体 SNAP25 基因是否与正常范围内智力能力的变化有关，该基因之前与智力能力的正常范围内的变异有关。SNAP25 的基因产物是一种重要的突触前质膜蛋白，已知参与调节神经递质的释放，并通过其对海马体的长时程增强作用与记忆和学习有关。SNAP25 中与智力能力相关的两个遗传变异的等位基因频率在 636 名 ID 病例（IQ<70）组和 361 名高于平均智力能力的对照组之间进行了比较。与对照组相比，病例组中假定的 rs363050 风险等位基因的频率更高（P=0.02；OR=1.24）。这些结果与 SNAP25 在 ID 中的作用一致，也支持 ID 反映智力能力定量分布的较低极端的观点。
