• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2002년도 제11차 추계학술대회
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• pp.7-7
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• 2002

• Journal of Pharmaceutical Investigation
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• 제37권6호
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• pp.369-376
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• 2007

Cyclosporine (CsA) and tacrolimus (FK506) have a narrow therapeutic range, and their pharmacokinetic (PK) characteristic varies among individual. They are also substrates for cytochrome P450 (CYP) 3A4, 3A5 genes, and P-glycoprotein, the product of the multidrug resistance 1 (MDR1). The aims were to investigate the relationship between CYP3A and MDR1 genotypes and their PK parameters among healthy subjects. We investigated the genotype for CYP3A and MDR1 gene in human using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. After oral administration of CsA and FK506 (100 mg and 1 mg, respectively), whole blood samples were taken up to 24 hours. Blood CsA and FK506 concentrations were measured by LC/MS/MS. Each PK parameters were compared using Kruskal-Wallis test according to the CYP3A and MDR1 genotype. We found that the values of AVC for CsA were significantly different among CYP3A5 and MDR1 exon 26 (C3435T) genotypes (P=0.037 and P=0.049). On the other hand, the AUC for FK506 was significantly different only among CYP3A5 genotypes (P=0.013). The results clearly demonstrate the effects of CYP3A5 and MDR1 exon 26 on Cys and FK506 disposition.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.238.2-239
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• 2003

The purposes of this study were to evaluate the relationship between the genetic polymorphisms in CYP2D6*10 allele, MDR1 (exon 21 and 26) gene and risperidone pharmacokinetics in healthy male Korean subjects. A single dose of 2 mg risperidone tablet was given orally to 23 healthy male Korean volunteers. Blood samples were taken during the 12 hours after the dose. Serum concentrations of risperidone and 9-hydroxyrisperidone were measured using HPLC with UV detector. 23 subjects were genotyped for CYP2D6*10 allele, MDR1 G2677 T and C3435T by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). (omitted)

• Tuberculosis and Respiratory Diseases
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• 제54권4호
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• pp.367-377
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• 2003

연구배경 : 결핵균에 감염된 사람 중 약 10%만이 임상적으로 발병하는 것으로 보아 결핵의 발병 감수성에 숙주의 유전적 인자가 작용할 것으로 생각되고 있다. 저자들은 한국인 폐결핵 환자를 대상으로 고해상도 HLA 형별검사를 이용한 대립유전자 수준의 HLA-DR 및 DQ 유전자의 연관성에 대해 분석해 보았다. 방 법 : 이전 결핵 치료력이 없는 결핵 환자 67명(약제감수성군 38명, 다제내성군 29명)과 200명의 정상대조군을 대상으로 하였으며 HLA-DRB1 형별검사는 reverse SSO (sequence specific oligonucleotide)와 PCR-SSCP (single strand conformational polymorphism) 방법으로, DQB1 형별검사는 PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP 및 PCR-SSP (sequence specific primer) 방법으로 시행하였다. 결 과 : 결핵환자군 중 다제내성군에서 대조군에 비해 DRB1*0701과 *08032의 빈도가 약 2배 정도 증가되는 경향을 보였고 이들 대립유전자와 연관된 DQB1*0202와 *0601(15.5% vs 34.5%, p=0.01)이 증가되었다. DQB1*0609는 결핵환자군에서 대조군에 비해 유의하게 증가되었고(4.0% vs 14.9%, p=0.004), 약제감수성군과 다제내성군에서 유사한 정도의 증가를 보였다. 폐병변의 중증도와 HLA의 연관성을 보면 덜 진행된 군(약제감수성군의 경증, 다제내성군의 중등증)에 비해 더 진행된 군(약제감수성군의 중등증+중증, 다제내성군의 중증)에서 DRB1*08032(4.2% vs 32.6%, p=0.007)와 DQB1*0601(12.5% vs 34.9%, p=0.047)이 유의하게 증가되었다. DQB1*0609는 다제내성군에서는 중증군에서, 약제감수성군에서는 경증군에서 대조군에 비해 유의하게 증가되었고 DRB1*0701과 DQB1*0202는 다제내성군의 중등증군에서만 유의하게 증가되어 이들 대립유전자는 폐병변의 중증도와 일정한 연관을 보이지는 않았다. 결 론 : HLA-DRB1*08032 및 DQB1*0601 대립유전자는 한국인에서 다제내성 결핵의 유전적 감수성인자로 생각되며 질환의 중증도와도 연관을 보이는 것으로 나타났다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1009-1014
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• 2016

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis.

• Tuberculosis and Respiratory Diseases
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• 제62권6호
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• pp.492-498
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• 2007

연구배경: 결핵균에 노출된 후 임상적 결핵으로 발병하는데 유전적 인자가 관여할 수 있으며, 치료 반응에도 숙주의 유전적 요인이 관여할 가능성이 있다. 이에 저자들은 NRAMP1 유전자 다형성을 감수성결핵과 다제내성결핵환자로 나누어서 비교하였다. 방 법: 100명의 약제감수성군, 102명의 다제내성군, 96명의 건강대조군을 대상으로 274C/T, 469+14G/C, 577-18G/A, 823C/T, A318V, 1465-85G/A, D543N, 1729+55del4 의 NRAMP1 유전자 다형성의 빈도를 중합효소 연쇄반응기법과 중합효소 연쇄반응-제한분절길이 다형성법을 이용하여 분석하였다. 결 과: NRAMP1 유전자의 D543N 이형접합체의 빈도는 건강대조군에 비해 약제감수성군에서 높았으나(OR=2.10, 95% CI=1.00 to 4.41, p=0.049) 다제내성군에서는 차이가 없었다. 823C/T의 이형접합체의 빈도는 건강대조군에 비해 약제감수성군(OR=2.79, 95% CI=1.11 to 7.04, p=0.029)과 다제내성군 (OR=3.30, 95% CI=1.33 to 8.18, p=0.010)에서 유의하게 높았으나 약제감수성군과 다제내성군 사이에는 유의한 차이가 없었다. 결 론: NRAMP1 유전자의 823C/T 이형접합체의 빈도는 약제감수성군과 다제내성군에서 유의하게 높아, 폐결핵의 발생과 연관되는 후보유전자일 가능성이 있으며 약제감수성결과에 따른 결핵이환에는 차이를 보이지 않았다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6953-6961
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• 2015

Background: Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol-associated head and neck cancer (HNC) susceptibility among the northeast Indian population. Materials and Methods: One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. Results: The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1. Conclusions: Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.27-29
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• 2004

Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2001년도 제10차 추계학술대회
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• pp.53-53
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• 2001

• Communications for Statistical Applications and Methods
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• 제16권1호
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• pp.67-74
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• 2009

고품질 한우를 만들기 위해 여러 경제형질에 영향을 주는 유전자 즉 single nucleotide polymorphisms(SNPs)를 규명하려고 한다. 이미 Lee 등 (2008a)에 의해 SNP(19_1)$^*$SNP(28_2)가 등심단면적 (LMA: longissimus muscle dorsi area)에 주요한 유전자로 규명되었다. 여기에 추가로 도체중 (CWT: carcass cold weight)과 일당증체량 (ADG: average daily gain)을 선형 모형에 적용하였으며 또한 상호작용에 더 유리하고 연속형 데이터에도 사용할 수 있는 expanded multifactor dimensionality reduction (expanded MDR)을 이용하여 주요한 SNP를 파악하였다. Expanded MDR 적용결과 등심단면적과 같은 결과인 SNP(19_1)과 SNP(19_1)$^*$SNP(28_2)의 상호작용 형태가 가장 좋은 SNP로 선정되었으며, 최종적으로 SNP(19_1)*SNP(28_2) 마커가 한우의 여러 경제형질에 우수 유전자임을 규명하였다.