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Assessment between Dopamine Receptor D2 (DRD2) Polymorphisms and Schizophrenia in Korean Population
조아랑,이상민,강원섭,김수강,정주호 대한정신약물학회 2012 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.10 No.2
Objective: The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of dopamine receptor D2(DRD2) are associated with schizophrenia in Korean population. Methods: Four SNPs (rs4648317, rs7131056, rs4936270, and rs1076562) of DRD2 were selected and genotyped by direct sequencing in 197 schizophrenia patients and 370 control subjects. SNPAnalyzer, SNPStats, and Haploview version 4.2 programs were performed to analyze the genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive,overdominant, and log-additive) were used to evaluate the odds ratios (ORs), 95% confidence intervals (CIs), and p values. For multiple testing, p values (pc) were re-evaluated by Bonferroni’s correction. Results: The genotype frequency of DRD2 rs4936270 SNP was associated with the development of schizophrenia (p=0.0007,OR=1.71, 95% CI=1.16-2.52 in the codominant1 model; p=0.011, OR=1.63, 95% CI=1.12-2.37 in the dominant model; p=0.035,OR=1.41, 95% CI=1.03-1.95 in the log-additive model). The allele frequency of rs4936270 was also associated with the development of schizophrenia (p=0.024, OR=1.45, 95% CI=1.05-1.98). After Bonferroni’s correction, the genotype distribution of rs4936270was still related to the development of schizophrenia (pc=0.0028 in the codominant1 model; pc=0.044 in the dominant model). A linkage disequilibrium block consisted of rs4648317, rs7131056, and rs4936270. The CAT haplotype frequency was different between schizophrenia and controls (p=0.039). Conclusion: These results suggest that DRD2 SNPs may be associated with the development of schizophrenia in Korean population.
조아랑,김영호,김범식 대한스트레스학회 2008 스트레스硏究 Vol.16 No.2
High levels of homocysteine promote oxidative stress, and aberrant homocysteine metabolism is linked to neurodevelopmental disorders including schizophrenia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. The present study was conducted to examine the association between the MTHFR gene and schizophrenia in Korean population. Subjects of 279 patients with schizophrenia and 296 healthy controls were recruited. We genotyped two single nucleotide polymorphisms (SNPs, rs2274976 and rs1801133) using the Illumina Sentrix Array Matrix chip and direct sequencing. The rs2274976 (Arg594Gln) is located on exon 12 of the MTHFR gene region, and the rs1801133 (Ala222Val) located on exon 5. For the analysis of genetic data, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was also used. Patients with schizophrenia were evaluated according to clinical manifestations using the Operational Criteria Checklist (OPCRIT). Two SNPs (rs2274976 and rs1801133) were not associated with schizophrenia. However, one SNP showed a significant association with one phenotype of psychotic symptoms. Running commanding voices, which could be clinically considered serious feature of auditory hallucinations, was different in the recessive model (p=0.018; p=0.036 after Bonferroni correction). Recently, rs59514310 replaces rs1801133 as new number (SNP database, BUILD 129). In present study, a significant association was observed between rs1801133 and running commanding voices. The result suggests that the MTHFR gene may be a susceptibility gene for schizophrenia with auditory hallucination. (Korean J Str Res 2008;16:85∼91)
피부감작능 평가 대체시험법간 위양성 및 위음성 화학물질에 대한 인체 세포주 활성화방법의 전수에 따른 예측력 평가
조아랑 ( Ahrang Cho ),여경욱 ( Kyenguk Yeo ),정미숙 ( Misook Jung ),이재희 ( Jaehee Lee ),양수정 ( Sujeong Yang ),( Ravi Gautam ),이기용 ( Giyong Lee ),조지훈 ( Jihun Jo ),( Manju Acharya ),( Anju Maharjan ),김창열 ( Changyu 한국동물실험대체법학회 2020 동물실험대체법학회지 Vol.14 No.1
The in vitro alternative assay for evaluating skin sensitizing potentials (SSP) called human Cell Line Activation Test (h-CLAT) has been recently adopted as an international test guideline. The present study was proceeded to pursue the domestic establishment and expansion of h-CLAT. The standard operational procedure was prepared in detail by the lead laboratory (LL) and transferred to one participating laboratory (PL). The LL demonstrated technical proficiency for the 10 substances listed in OECD TG 442E. The PL also demonstrated a certain level of proficiency, in that 4-phenylenediamine and 4-aminobenzoic acid distributed with coded names were correctly classified as positive and negative on SSP, respectively, and other indices including 75% cell viability (CV75) and relative fluorescence intensity (RFI) % for CD54 and CD86 were fell within the reference range. Methyl methacrylate, nickel chloride, and resorcinol, which are inconsistent in predicting SSP through various alternative test methods, were unanimously predicted as negative, positive, and positive on SSP by the two laboratories for the first time through h-CLAT. Both chlorobenzene and sodium lauryl sulfate with the existing h-CLAT report as positive and negative, respectively, were predicted as negative by the PL, which could contribute toward overall categorization into non-skin sensitizer.
Ah Rang Cho(조아랑),Jin Kyung Park(박진경),Jong Woo Kim(김종우),Ji Young Song(송지영),Joo Ho Chung(정주호),Geon Ho Bahn(반건호) 대한생물치료정신의학회 2007 생물치료정신의학 Vol.13 No.1
목적 : Dopamine beta-hydroxylase(DBH) 유전자는 정신병적 증상과 관련하여 정신분열병의 후보유전자 중의 하나이다. 본 연구는 DBH 유전자 내 새로운 단일염기다형성의 유전자형을 확인하고 정신분열병과의 유전적 연관성을 알아보고자 하였다. 연구대상 및 방법 : DSM-Ⅳ에 의해 정신분열병으로 진단된 입원환자 89명과 정신질환의 과거력과 가족력이 없는 대조군 109명을 대상으로 하였다. DBH 유전자의 네 번째 엑손 부위를 다중효소중합연쇄반응(Polymerase Chain Reaction, PCR)으로 증폭하여 DNA sequencing 기법으로 유전자형을 확인하고 연관성을 알아보기 위한 통계 분석을 시행하였다. 결과 : DBH 유전자 내 4개의 단일염기다형성(DBH5818G/A, DBH5990G/A, DBH6153C/T, DBH6259A/G)을 확인하였다. 이 4개의 단일염기다형성 모두에서 정신분열병 환자군과 정상 대조군 간 유전자형 분포와 대립유전자 빈도 및 일배체형 빈도에서의 유의한 차이는 없었다. DBH와의 관련성이 보고된 양성 정신병적 증상이 두드러지는 편집형 정신분열병 환자군과 정상 대조군 간 일배체형 빈도에서도 유의한 차이는 보이지 않았다. 결론 : DBH5818G/A, DBH5990G/A, DBH6153C/T, 그리고 DBH6259A/G 다형성은 한국 정신분열병 환자군과 유전적 관련성이 없을 것으로 추정된다.
박해정,조아랑,박진경,강원섭 대한스트레스학회 2010 스트레스硏究 Vol.18 No.3
Clozapine, an atypical antipsychotic agent, has proven to be effective in the treatment of refractory schizophrenia. As the idiosyncratic clozapine-induced adverse effects such as dyslipidemia and agranulocytosis occur in 0.5∼2% of the treated patients, the use of clozapine has been limited. In this study, we assessed the patterns of gene regulation by clozapine (10μM, 24 h) in SH-SY5Y human neuroblastoma cells through microarray analysis. Clozapine upregulated the expressions of 165 genes, and downregulated the expressions of 305 genes. Of these genes, clozapine potently increased the level of chemokine (C-C motif) ligand 3 gene (CCL3, 15.596-fold) and decreased the level of retinoic acid early transcript 1E (RAET1E, 0.171-fold). Both of these genes belong to the category of immune response-related genes. We also found the changes of the expressions of immune response-related genes were most remarkable. Especially, clozapine increased the levels of chemokine genes, such as CCL3 (also known as MIP-1α), CCL2 (also known as MCP-1), and chemokine (C-C motif) receptor 3 (CCR3). This result may contribute to understanding of adverse effects of clozapine. (Korean J Str Res 2010;18:229∼235) 비정형 항정신병 치료제인 clozapine은 정신분열병 치료에 매우 효과적인 약물이다. 그러나 clozapine으로 치료 받는 환자의 0.5∼2%에서 무과립구증과 같은 면역계 관련 부작용이 발생한다고 보고되어 왔으며, 따라서 clozapine의 사용은 제한되어 왔다. 본 연구는 microarray 분석법을 이용하여 사람 SH-SY5Y neuroblastoma 세포에서 clozapine (10μM, 24 h)에 의해 변화되는 유전자의 발현 양상을 알아보고자 하였다. 실험 결과, clozapine에 의해 165개의 유전자 발현이 증가하였으며, 306개의 유전자 발현이 감소하였다. 특히, 면역 관련 유전자의 발현 변화가 현저했으며, chemokine (C-C motif) ligand 3 (CCL3, 15.596-fold)가 가장 크게 증가하였고, retinoic acid early transcript 1E (RAET1E, 0.171-fold)가 가장 크게 감소하는 것을 확인하였다. Clozapine은 특히 CCL3 (MIP-1α), CCL2 (MCP-1) 및 CCR3과 같은 chemokine 유전자의 발현을 증가시켰다. 이러한 결과는 clozapine의 면역계 관련 부작용에 대한 기전을 이해하는데 중요한 자료를 제시할 것으로 생각한다.