Nerve growth factor and its receptor in schizophrenia.

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 rs6330*T and NGFR rs11466155*T, rs2072446*T alleles might be nominated as risk factors, whereas the NGF rs4839435*A and NGFR rs734194*G alleles might be protective against developing schizophrenia.

Association of C1QB gene polymorphism with schizophrenia in Armenian population.

BACKGROUND: Schizophrenia is a complex, multifactorial psychiatric disorder. Our previous findings indicated that altered functional activity of the complement system, a major mediator of the immune response, is implicated in the pathogenesis of schizophrenia. In order to explore whether these alterations are genetically determined or not, in the present study we evaluated the possible association of complement C1Q component gene variants with susceptibility to schizophrenia in Armenian population, focusing on four frequent single nucleotide polymorphisms (SNPs) of C1QA and C1QB genes. METHODS: In the present study four SNPs of the complement C1Q component genes (C1QA: rs292001, C1QB rs291982, rs631090, rs913243) were investigated in schizophrenia-affected and healthy subjects. Unrelated Caucasian individuals of Armenian nationality, 225 schizophrenic patients and the same number of age- and sex-matched healthy subjects, were genotyped. Genotyping was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP) and quantitative real-time (qRT) PCR methods. RESULTS: While there was no association between C1QA rs292001, C1QB rs913243 and rs631090 genetic variants and schizophrenia, the C1QB rs291982*G minor allele was significantly overrepresented in schizophrenic patients (G allele frequency 58%) when compared to healthy subjects (46%, OR = 1.64, p(corr) = 0.0008). Importantly, the susceptibility for schizophrenia was particularly associated with C1QB rs291982 GG genotype (OR = 2.5, p(corrected) = 9.6E-5). CONCLUSIONS: The results obtained suggest that C1QB gene may be considered as a relevant candidate gene for susceptibility to schizophrenia, and its rs291982*G minor allele might represent a risk factor for schizophrenia at least in Armenian population. Replication in other centers/populations is necessary to verify this conclusion.

Functional variants of the genes involved in neurodevelopment and susceptibility to schizophrenia in an Armenian population.

Aberrant neurodevelopment contributes to the etiology of schizophrenia. This study aimed to investigate the potential association of netrin G1 (NTNG1) rs628117 and brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) genetic polymorphisms with susceptibility to schizophrenia. One hundred three Armenian patients with schizophrenia and 105 healthy control subjects were genotyped by polymerase chain reaction with sequence-specific primers. Whereas the NTNG1 rs628117 genotypes were equally distributed in the groups, the carriers of the less common BDNF 66Met allele were overrepresented among patients with schizophrenia when compared with healthy controls (55% vs 35%, odds ratio = 2.28, 95% confidence interval 1.14-1.98, p(corrected) = 0.006). Furthermore, the 66Met/Met genotype correlated with earlier disease onset (p = 0.024). In conclusion, our single-cohort study nominates the BDNF 66Met allele as a risk factor for schizophrenia in an Armenian population. This must be confirmed in other Armenian cohorts.