Zakharyan Roksana, Atshemyan Sofi, Gevorgyan Anaida, Boyajyan Anna
Institute of Molecular Biology, National Academy of Sciences of the Republic of Armenia (NAS RA), 7 Hasratyan St., 0014 Yerevan, Armenia.
Nork Clinic attached to the Psychiatric Medical Center of the Ministry of the Health of the Republic of Armenia, 2a Hovsepyan St., 0047 Yerevan, Armenia.
BBA Clin. 2014 May 20;1:24-9. doi: 10.1016/j.bbacli.2014.05.001. eCollection 2014 Jun.
Promising studies suggest that defects in synaptic plasticity detected in schizophrenia may be linked to neurodevelopmental and neurodegenerative abnormalities and contribute to disease-associated cognitive impairment. We aimed to clarify the role of the synaptic plasticity regulatory proteins, nerve growth factor (NGF) and its receptor (NGFR) in the pathogenesis of schizophrenia by comparative analysis of their blood levels and functional single nucleotide polymorphisms (SNPs) in genes encoding these proteins (NGF and NGFR) in schizophrenia-affected and healthy subjects. Relationships between the selected SNPs' genotypes and NGF and NGFR plasma levels were also assessed. Our results demonstrated a positive association between schizophrenia and the NGF rs6330 as well as the NGFR rs11466155 and rs2072446 SNPs. Also, a negative association between this disorder and NGF rs4839435 as well as NGFR rs734194 was found. In both, haloperidol-treated and antipsychotic-free patients decreased blood levels of the NGF and NGFR were found, and a positive interrelation between rs6330 and rs2072446 carriage and decreased NGF and NGFR levels, respectively, was revealed. In conclusion, our results demonstrate association of schizophrenia with the rs6330, rs4839435 and rs734194, rs11466155, rs2072446 as well as with the decreased blood levels of corresponding proteins. Our findings indicate the implication of alterations in NGFR and NGFR genes in schizophrenia, particularly, in defects of synaptic plasticity. Furthermore, the data obtained suggests that at least in Armenian population the NGF rs6330T and NGFR rs11466155T, rs2072446T alleles might be nominated as risk factors, whereas the NGF rs4839435A and NGFR rs734194*G alleles might be protective against developing schizophrenia.
有前景的研究表明，在精神分裂症中检测到的突触可塑性缺陷可能与神经发育和神经退行性异常有关，并导致疾病相关的认知障碍。我们旨在通过比较精神分裂症患者和健康受试者血液中神经生长因子（NGF）及其受体（NGFR）的水平以及编码这些蛋白质（NGF和NGFR）的基因中的功能性单核苷酸多态性（SNP），来阐明突触可塑性调节蛋白在精神分裂症发病机制中的作用。还评估了所选SNP的基因型与NGF和NGFR血浆水平之间的关系。我们的结果表明，精神分裂症与NGF的rs6330以及NGFR的rs11466155和rs2072446 SNP之间存在正相关。此外，还发现该疾病与NGF的rs4839435以及NGFR的rs734194之间存在负相关。在接受氟哌啶醇治疗和未使用抗精神病药物的患者中，均发现NGF和NGFR的血液水平降低，并且分别揭示了rs6330和rs2072446携带与NGF和NGFR水平降低之间的正相关关系。总之，我们的结果表明精神分裂症与rs6330、rs4839435和rs734194、rs11466155、rs2072446以及相应蛋白质血液水平降低有关。我们的研究结果表明NGF和NGFR基因的改变与精神分裂症有关，特别是与突触可塑性缺陷有关。此外，获得的数据表明，至少在亚美尼亚人群中，NGF的rs6330T和NGFR的rs11466155T、rs2072446T等位基因可能被视为危险因素，而NGF的rs4839435A和NGFR的rs734194*G等位基因可能对精神分裂症的发生具有保护作用。
