| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Jun 147B: 491-4 |
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| PMID | 18085566 |
| Title | Pharmacogenetic study of atypical antipsychotic drug response: involvement of the norepinephrine transporter gene. |
| Abstract | The identification of genetic factors underlying individual differences in antipsychotic drug response is of major interest. We investigated the involvement of two norepinephrine transporter gene polymorphisms in response to antipsychotics, comparing patients with strong and weak response to olanzapine and risperidone. We prospectively assessed short-term drug response in 75 Caucasian schizophrenic patients treated with these drugs, using the Positive and Negative Syndrome Scale. We then assessed the association between two SLC6A2 gene polymorphisms and drug response in this sample. No significant difference in genotype distribution was found between responders and non-responders, for the G1287A or T-182C polymorphism. The improvement in PANSS positive subscore was significantly greater in patients homozygous for the A1287 allele than in other patients, and significantly smaller in patients homozygous for the C-182 allele than in other patients. Our results suggest that these polymorphisms are specifically involved in the variation of positive symptoms in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Pharmacogenet. Genomics 2011 Apr 21: 197-205 |
| PMID | 20818294 |
| Title | A possible association of the norepinephrine transporter gene in the development of heroin dependence in Han Chinese. |
| Abstract | Noradrenergic pathways have been suggested to play a crucial role in the motivation-reward system of heroin dependence (HD), but so far, the role of the human norepinephrine transporter (NET; SLC6A2) gene in the pathogenesis of HD has never been investigated. The purpose of this study was to examine whether the NET gene is associated with the development of HD, and whether the NET gene influences specific personality traits. Twelve single-nucleotide polymorphisms of the NET gene were analyzed in a case-control study of 965 Han Chinese participants (603 patients and 362 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and schizophrenia-Lifetime and all patients met the criteria for HD. A Chinese version of the Tridimensional Personality Questionnaire was used to assess personality traits and examine the association between specific personality traits and NET polymorphisms. No statistically significant differences in allele or genotype frequencies were observed in any of the investigated NET variants between HD patients and controls. After logistic regression analyses, no statistically significant effect of NET variants in the development of HD was found. In haplotype analysis, the frequency of AATA haplotype in rs1532701-rs40434-rs13333066-rs187714 was significantly different between HD patients and controls. These NET polymorphisms did not influence novelty seeking and harm avoidance scores. This study suggests that the NET gene may be associated with the development of HD, but not associated with specific personality traits among Han Chinese. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Pharmacogenomics J. 2015 Aug -1: -1 |
| PMID | 26282453 |
| Title | Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population. |
| Abstract | schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychiatry Investig 2015 Oct 12: 551-8 |
| PMID | 26508968 |
| Title | Association Study between Norepinephrine Transporter Gene Polymorphism and Schizophrenia in a Korean Population. |
| Abstract | We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia. Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline. We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms. Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results. |
| SCZ Keywords | schizophrenia, schizophrenic |