Nabil Fikri Rahim Mohd, Norlelawati A Talib, Nour El-Huda Abdul Rahim, Hanisah Mohd Noor, Kartini Abdullah, Norsidah Kuzaifah, Nor Zamzila Abdullah
Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia, Malaysia.
Department of Pathology & Laboratory Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Malaysia.
J Psychiatr Res. 2017 May;88:28-37. doi: 10.1016/j.jpsychires.2016.12.020. Epub 2017 Jan 1.
The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.
与多巴胺能神经元发育相关的RELN表观遗传变化可能符合精神分裂症的发育理论。然而，关于RELN DNA甲基化与精神分裂症关联的证据还远远不够充分，因为相关研究仅在少数有限的脑样本上进行。由于外周血中的DNA甲基化可能反映大脑中发生的变化，鉴于脑样本稀缺，利用外周血进行精神分裂症的DNA甲基化研究是可行的。因此，我们研究的目的是使用来自该疾病患者外周血的基因组DNA，检测RELN启动子的DNA甲基化水平与精神分裂症之间的关系。病例对照研究包括从同一地区招募的110名精神分裂症参与者和122名健康对照。经过亚硫酸氢盐转化后，根据使用高灵敏度实时MethyLight TaqMan程序检测的Cq值差异计算DNA样本的甲基化水平。与对照组相比，精神分裂症患者中RELN启动子的甲基化水平显著更高（p = 0.005），男性与女性相比也是如此（p = 0.004）。随后，甲基化组的RELN表达比未甲基化组低25倍。基于大脑和外周血中平行甲基化变化的假设，我们得出结论，RELN DNA甲基化可能参与精神分裂症的发病机制。然而，甲基化在发育过程以及成年期对RELN功能的确切影响仍需要进一步阐述。
