Lochman Jan, Plesník Jiří, Janout Vladimír, Povová Jana, Míšek Ivan, Dvořáková Dagmar, Šerý Omar
Laboratory of Neurobiology and Molecular Psychiatry, Laboratory of Molecular Physiology, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
Neuro Endocrinol Lett. 2013;34(8):792-7.
Increasing evidences support the importance of epigenetic control in schizophrenia pathogenesis. One of the enzymes involved in DNA methylation process through homocysteine metabolism is methylenetetrahydrofolate reductase (MTHFR). The most extensively studied variant in the MTHFR gene is the C677T polymorphism, resulting in reduced enzyme activity and elevated homocysteine level.
In sample of 192 schizophrenics and 213 healthy controls an increasing risk of schizophrenia associated with MTHFR 677 CT+TT genotype was found (OR=1.6, p=0.021). Association was also evaluated by considering the C677T polymorphism as an interaction with COMT Val158Met and ADRA2A C-1291G polymorphisms previously associated with schizophrenia risk using a logistic regression analysis.
Previous studies of MTHFRCOMT (C677TVal158Met) interaction in relation to schizophrenia resulted in inconsistent results. In our sample this interaction did not significantly differ between schizophrenics and control subjects. On the other hand analysis of MTHFRADRA2A (C677TC-1291G) interaction revealed significant association between ADRA2A CC+CG genotype in the MTHFR TC+TT carriers (p=0.008).
Our results support role of noradrenergic functions as well as previously proposed role of epigenetic control in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to prove our results.
越来越多的证据支持表观遗传调控在精神分裂症发病机制中的重要性。通过同型半胱氨酸代谢参与DNA甲基化过程的一种酶是亚甲基四氢叶酸还原酶（MTHFR）。MTHFR基因中研究最广泛的变异是C677T多态性，它会导致酶活性降低和同型半胱氨酸水平升高。
在192例精神分裂症患者和213例健康对照的样本中，发现MTHFR 677 CT+TT基因型与精神分裂症风险增加相关（比值比=1.6，p=0.021）。还通过逻辑回归分析，将C677T多态性视为与先前与精神分裂症风险相关的COMT Val158Met和ADRA2A C-1291G多态性的相互作用来评估关联性。
先前关于MTHFRCOMT（C677TVal158Met）相互作用与精神分裂症关系的研究结果不一致。在我们的样本中，这种相互作用在精神分裂症患者和对照受试者之间没有显著差异。另一方面，对MTHFRADRA2A（C677TC-1291G）相互作用的分析显示，在MTHFR TC+TT携带者中，ADRA2A CC+CG基因型之间存在显著关联（p=0.008）。
我们的结果支持去甲肾上腺素能功能的作用以及先前提出的表观遗传调控在精神分裂症发病机制中的作用。需要进一步开展包括更大样本量和更多标记物的相关研究来证实我们的结果。
