Association Study of Polymorphisms in Neuronal Nicotinic Acetylcholine Receptor Subunit Genes With Schizophrenia in the Han Chinese Population

Objective@#To investigate the relation between nicotinic acetylcholine receptor subunit (nAChR) genes and schizophrenia, and the relation between tag single nucleotide polymorphism (rs1317286, rs1044396, rs6494212, rs16969968, and rs684513) and schizophrenia in Han Chinese people. @*Methods@#The protein-protein interaction (PPI) network among nAChR protein and 350 proteins encoded by schizophrenia-related susceptibility genes was constructed through the String database to explore whether nAChR genes were associated with schizophrenia in these known databases. Then, five single nucleotide polymorphisms (SNPs) of CHRNA3 (rs1317286), CHRNA4 (rs1044396), CHRNA7 (rs6494212), and CHRNA5 (rs16969968, rs684513) were analyzed in a sample of 1,035 schizophrenic patients and 816 healthy controls. The interaction between the markers was analyzed using multifactor dimensionality reduction (MDR) software. Power analysis was performed using the Quanto program. @*Results@#There are no significant differences in genotype or allele distribution were identified between the patients and controls (p>0.05). The haplotypes constructed by four markers rs1317286, rs6494212, rs16969968, and rs684513 were not associated with schizophrenia either. However, a significant association between models made of rs1317286, rs1044396, rs6494212, and rs684513 and schizophrenia was revealed in interaction analysis (p<0.05). @*Conclusion@#The nAChR protein may have effects on the development of schizophrenia through the interaction with proteins encoded by schizophrenia-related susceptibility genes, but no relation was found between selected polymorphisms and schizophrenia in the collected Han Chinese people. However, interaction analysis suggested four-SNP model has an important effect on schizophrenia.

Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs).</p><p><b>METHODS</b>A total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD.</p><p><b>RESULTS</b>The distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents.</p><p><b>CONCLUSIONS</b>It is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.</p>

Association of cyclic adenosine monophosphate response element-binding protein gene and major depressive disorder / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD).</p><p><b>METHODS</b>We recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed.</p><p><b>RESULTS</b>No significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022).</p><p><b>CONCLUSION</b>The rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.</p>

Association of DNA methyltransferase 3B gene polymorphism with early-onset schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of DNA methyltransferase 3B (DNMT3B) gene polymorphism with the development of early-onset schizophrenia.</p><p><b>METHODS</b>A single nucleotide polymorphism (rs6119954) of DNMT3B gene was genotyped in 279 early-onset schizophrenic patients and 395 healthy controls, using TaqMan SNP Genotyping Assays. To detect the interaction between the DNMT3B gene and environmental factors, the prenatal information of the patients was collected.</p><p><b>RESULTS</b>Genotype distribution of the rs6119954 locus was significantly different between patients and controls (Chi-square = 12.27, P< 0.01). The frequency of the G allele of this locus was significantly higher in patients than in controls (Chi-square = 12.76, P< 0.01). The G allele was highly associated with an earlier age of onset (P= 0.026). No interaction between the DNMT3B gene and environmental factors was found.</p><p><b>CONCLUSION</b>DNMT3B gene is associated with early-onset schizophrenia and rs6119954 may plays an important role in age of onset of schizophrenia.</p>