Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
Laboratory of Neurobiology and Pathological Physiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic.
J Clin Lab Anal. 2023 Jul;37(13-14):e24949. doi: 10.1002/jcla.24949. Epub 2023 Jul 28.
Insulin-degrading enzyme (IDE) is an important gene in studies of the pathophysiology of type 2 diabetes mellitus (T2DM). Recent studies have suggested a possible link between type 2 diabetes mellitus (T2DM) and the pathophysiology of schizophrenia (SZ). At the same time, significant changes in insulin-degrading enzyme (IDE) gene expression have been found in the brains of people with schizophrenia. These findings highlight the need to further investigate the role of IDE in schizophrenia pathogenesis.
We enrolled 733 participants from the Czech Republic, including 383 patients with schizophrenia and 350 healthy controls. Our study focused on the single nucleotide polymorphism (SNP) rs2421943 in the IDE gene, which has previously been associated with the pathogenesis of Alzheimer's disease. The SNP was analyzed using the PCR-RFLP method.
The G allele of the rs2421943 polymorphism was found to significantly increase the risk of developing SZ (p < 0.01) when a gender-based analysis showed that both AG and GG genotypes were associated with a more than 1.55 times increased risk of SZ in females (p < 0.03) but not in males. Besides, we identified a potential binding site at the G allele locus for has-miR-7110-5p, providing a potential mechanism for the observed association.
Our results confirm the role of the IDE gene in schizophrenia pathogenesis and suggest that future research should investigate the relationship between miRNA and estrogen influence on IDE expression in schizophrenia pathogenesis.
胰岛素降解酶（IDE）是 2 型糖尿病（T2DM）病理生理学研究中的一个重要基因。最近的研究表明，2 型糖尿病（T2DM）和精神分裂症（SZ）的病理生理学之间可能存在联系。同时，在精神分裂症患者的大脑中发现了胰岛素降解酶（IDE）基因表达的显著变化。这些发现强调了需要进一步研究 IDE 在精神分裂症发病机制中的作用。
我们从捷克共和国招募了 733 名参与者，包括 383 名精神分裂症患者和 350 名健康对照者。我们的研究集中在 IDE 基因中的单核苷酸多态性（SNP）rs2421943，该 SNP 先前与阿尔茨海默病的发病机制有关。使用 PCR-RFLP 方法分析 SNP。
当基于性别的分析表明，AG 和 GG 基因型都与女性 SZ 的风险增加 1.55 倍以上（p < 0.03），而与男性无关时，发现 rs2421943 多态性的 G 等位基因显著增加了 SZ 的发病风险（p < 0.01）。此外，我们在 G 等位基因座处鉴定出一个潜在的结合位点，用于 has-miR-7110-5p，为观察到的关联提供了潜在的机制。
我们的结果证实了 IDE 基因在精神分裂症发病机制中的作用，并表明未来的研究应调查 miRNA 和雌激素对精神分裂症发病机制中 IDE 表达的影响之间的关系。
