네 시의 발문

최지하 고요아침 2016 열린시학 Vol.21 No.1

OCT2 수송체 근위 프로모터 부위의 새로운 유전자 변이 발굴

최지하 이화여자대학교 의과대학 2011 EMJ (Ewha medical journal) Vol.34 No.1

목 적 유기 양이온 수송체 2(OCT2, SLC22A2)는 신장의 근위 세뇨관 세포에 많이 발현되어 있으면서 내인성 또는 외인성(약물 포함) 물질들의 신장 내 제거에 중요한 역할을 한다. 본 연구는 OCT2의 근위 프로모터 부위의 유전자 변이를 찾기 위하여 시행되었다. 방 법 다양한 인종으로 구성된 272명의 게놈 DNA을 이용한 직접적인 시퀀싱 방법을 통해 OCT2 프로모터 부위의 유전자 변이를 검색하였다. 프로모터 활성은 ACHN, HCT-116 세포를 이용한 dual luciferase assay 기법을 통하여 측정하였다. 결 과 OCT2 근위 프로모터 부위에서 총 4개의 유전자 변이를 발견하였으며 모든 유전자 변이는 다형성(적어도 한 인종군에서 마이너 대립유전자 빈도>1%)을 나타냈다. 프로모터 활성을 측정한 결과 g.-246C>T 변이는 유의하게 감소된 활성(38%, p<0.001)을 보였고, 또 다른 변이인 g.-47C>T는 유의하게 증가된 활성(10%, p<0.05)을 나타냈다. 결 론 본 연구는 OCT2유전자의 전사를 조절하는 새로운 유전자 변이를 밝혀냈다. 이러한 유전자 변이는 궁극적으로 OCT2의 기질인 많은 약물들의 약동학 혹은 약물반응에 영향을 끼칠 수 있을 것이다. Objectives:Human organic cation transporter 2, OCT2(SLC22A2), highly expressed on the renal proximal tubular cells, plays an important role in the renal excretion of endogenous and exogenous organic cations including many therapeutic drugs. This study was performed to identify genetic variations in the proximal promoter region of OCT2. Methods:The promoter region of OCT2 was amplified and directly sequenced from genomic DNA samples from individuals of diverse ethnicities(n=272). The promoter activity of OCT2 was measured using a luciferase reporter assay in two cell lines ; ACHN, and HCT-116. Results:There were four polymorphic(minor allele frequency >1% in at least one of the four ethnic groups) variants in the OCT2 promoter region(-250/+60 from the transcription start site). One(V2, g.-246C>T) of them showed decreased reporter activity by 38%(p < 0.001), whereas another one(V4, g.-47C>T) showed increased activity by 10%(p< 0.05), compared to the reference in HCT-116 cell line. Conclusion:This study revealed that novel promoter variants of OCT2 results in changes in transcriptional activity of this gene. These variants can potentially affect the pharmacokinetics or drug response of many drugs that are substrates of OCT2.

시간 여행자를 위한 가이드

최지하 문예운동사 2020 문예운동 Vol.- No.148

Development of a Paste-type Certified Reference Material of Tomato for Elemental Analysis: Certification and Long-term Stability Study

최지하,황의진,임용현,조항미,임영란,김태규,이경석 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.2

A paste-type certified reference material (CRM) of tomato was developed for accurate elemental analysis of canned foods. Accurate mass fractions of cadmium (Cd), lead (Pb), and tin (Sn) in the tomato paste CRM were determined by isotope dilution inductively coupled plasma mass spectrometry. The certified values and their expanded uncertainties (k=2 at approximately 95% level of confidence) for Cd, Pb, and Sn were (0.297 ± 0.015) mg/kg, (0.213 ± 0.010) mg/kg, and (221.2 ± 9.5) mg/kg, respectively. Homogeneity of the CRM was 0.3%, 1.8%, and 0.2% for Cd, Pb, and Sn, respectively, which were estimated using the relative standard deviation of the measurement results of 10 separate sample bottles from one batch of the CRM. Major contributions to the measurement uncertainties for Cd and Sn were the uncertainties of the isotope ratios of Cd and Sn in the sample and the elemental standards. The uncertainty for Pb was mainly affected by sample homogeneity. Stability tests were conducted for 6 and 12 months at −20, 4, and 25°C, and the storage temperature for the CRM was determined to be −20°C. To investigate long-term storage, the mass fractions of Cd, Pd, and Sn in the CRM were re-determined after storage for 7 years. The results were in good agreement with the certified results implying that this CRM is stable for 7 years if kept at an appropriate storage condition with vacuum packaging the amber glass bottles in aluminum-coated polymer bag.

ABC 수송단백과 약물수송

최지하,이민구,Choi, Ji-Ha,Lee, Min-Goo 대한임상약리학회 2003 Translational and Clinical Pharmacology Vol.11 No.2

The ATP-binding cassette (ABC) transporters are involved in a variety of biologic processes in human and other organisms. Currently, 49 ABC transporter genes were identified in human genome and classified into 7 subfamilies according to their sequence homologies. The ABC proteins provide nutrients to the cells, protect them from a wide range of toxic compounds, and regulate basic biologic processes of essential organs such as alimentary tract, liver, lung and immune systems. Consequently, mutations affecting ABC-transporters have been found to be the underlying causes for a large number of human inherited diseases and individual diversity of drug responses. For example, aberrant membrane transport caused by mutations in CFTR gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. A group of ABC genes code the multi-drug resistance (MDR) and multidrug resistance-related proteins (MRPs) , which function as xenobiotic transporters. MDRI was originally identified as a gene that confers multi-drug resistance to cancer cells. The MRPs were discovered as a second type of drug pump in cancer cells exhibiting multi-drug resistance not caused by MDRl. However, recently it was found that they are the native exporters having physiological role of protecting organism from various toxic substances including commonly prescribed medications. Thus, identifying the individual genetic variations of these transporters carries significant meaning in pharmacotherapy of post-genomic era, since such genetic variants are likely to be an important source for the inter-individual variability in pharmacokinetics and pharmacodynamics of many drugs. Future investigations in large scale analysis of ABC transporter genes will provide the basis for understanding the pathogenesis of many genetic disorders and for elucidating the molecular mechanisms related to individual diversity of drug responses.

Gold Electroforming System을 이용한 하악 임플란트 지지 텔레스코프 피개의치

최지하(Jee-Ha Choi),김승균(Seung-Kyun Kim),유병일(Byoung-Il Yu),안승근(Seung-Geun Ahn),박주미(Ju-Mi Park),송광엽(Kwang-Yeob Song),박찬운(Charn-Woon Park) 대한턱관절교합학회 2008 구강회복응용과학지 Vol.24 No.2

Association study between OCTN1 functional haplotypes and Crohn’s disease in a Korean population

정은석,최지하,천재희,박효진,공경애 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.1

Crohn’s disease (CD) is a chronic inflammatory bowel disease with multifactorial causes including environmental and genetic factors. Several studies have demonstrated that the organic cation/carnitine transporter 1 (OCTN1) nonsynonymous variant L503F is associated with susceptibility to CD. However, it was reported that L503F is absent in Asian populations. Previously, we identified and functionally characterized genetic variants of the OCTN1 promoter region in Koreans. In that study, four variants demonstrated significant changes in promoter activity. In the present study, we determined whether four functional variants of the OCTN1 promoter play a role in the susceptibility to or clinical course of CD in Koreans. To examine it, the frequencies of the four variants of the OCTN1 promoter were determined by genotyping using DNA samples from 194 patients with CD and 287 healthy controls. Then, associations between genetic variants and the susceptibility to CD or clinical course of CD were evaluated. We found that susceptibility to CD was not associated with OCTN1 functional promoter variants or haplotypes showing altered promoter activities in in vitro assays. However, OCTN1 functional promoter haplotypes showing decreased promoter activities were significantly associated with a penetrating behavior in CD patients (HR=2.428, p=0.009). Our results suggest that the OCTN1 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease.

Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in Patients with Thyroid-Associated Ophthalmopathy

박효진,최지하,김주희,윤진숙,최양지,최윤희,국경훈 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.6

Purpose: This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Koreanpatients with thyroid-associated ophthalmopathy (TAO). Materials and Methods: Genetic analyses were conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48) to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of each genetic variant on the transcription or expression of these genes was examined. Additionally, correlations between functional haplotypes of ST3GAL5 or ST8SIA1 and clinical characteristics of the patients were investigated. Results: Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified, and four major promoter haplotypes were assembled. Additionally, three promoter variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and ST8SIA1 variants identified in TAO patients were also found in healthy controls. Promoter activity was significantly decreased in three promoter haplotypes of ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors activating protein-1, NKX3.1, and specificity protein 1 were revealed as having roles in transcriptional regulation of these haplotypes. The nonsynonymousvariant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no differences in clinical characteristics were detected in patients possessing the functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly lower in patients with the ST8SIA1 haplotype, which showed a significant increase in promoter activity. Conclusion: These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoterhaplotype and the clinical severity of TAO. However, further studies with larger sample sizes are warranted.

Identification and Functional Characterization of Novel Genetic Variations in the OCTN1 Promoter

박효진,최지하 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.2

Human organic cation/carnitine transporter 1 (OCTN1) plays an important role in the transport ofdrugs and endogenous substances. It is known that a missense variant of OCTN1 is significantlyassociated with Crohn’s disease susceptibility. This study was performed to identify genetic variantsof the OCTN1 promoter in Korean individuals and to determine their functional effects. First, thepromoter region of OCTN1 was directly sequenced using genomic DNA samples from 48 healthyKoreans. OCTN1 promoter activity was then measured using a luciferase reporter assay in HCT-116cells. Seven variants of the OCTN1 promoter were identified, two of which were novel. There werealso four major OCTN1 promoter haplotypes. Three haplotypes (H1, H3, and H4) showed decreasedtranscriptional activity, which was reduced by 22.9%, 23.0%, and 44.6%, respectively (p< 0.001),compared with the reference haplotype (H2). Transcription factor binding site analyses and gel shiftassays revealed that NF-Y could bind to the region containing g.-1875T>A, a variant present in H3,and that the binding affinity of NF-Y was higher for the g.-1875T allele than for the g.-1875A allele. NF-Y could also repress OCTN1 transcription. These data suggest that three OCTN1 promoterhaplotypes could regulate OCTN1 transcription. To our knowledge, this is the first study to identifyfunctional variants of the OCTN1 promoter.

III급 악골 관계를 가진 상악 편악 무치악 환자의 수복

박미희,홍준원,최지하,이정준,박주미,송광엽,안승근,Park, Mi-hee,Hong, Jun-won,Choi, Jee-ha,Lee, Jung-jun,Park, Ju-mi,Song, Kwang-yeob,Ahn, Seung-geun 대한턱관절교합학회 2009 구강회복응용과학지 Vol.25 No.4

심한 치조골 흡수를 동반한 III급 악골 관계 환자의 총의치 제작의 경우 안정적이고 지속적인 교합을 제공하는 치료계획을 세워야 한다. 불리한 치관 대 치근 비와 임상적 동요도가 관찰되는 하악 잔존치를 고정하여 사용함으로써 환자의 불편감을 줄이고 시간적, 경제적으로 효율적인 치료를 제공할 수 있다. 본 증례에서는 상악 편악 무치악 환자의 기능적인 하악 운동과 조화로운 총의치 균형 교합을 이루기 위해 T-Scan System을 이용하였다. In a case of class III skeletal patients with severe alveolar bone resorption, it must be a complete denture treatment plan provided stable and durable occlusion. Despite a markedly increased tooth mobility and unfavorable crown-to-root ration due to periodontal tissue breakdown, if the inflammatory process is controlled and an adequate oral hygiene performed, fixed splints will be considered. Patient's discomfort will be eliminated by achievement better clinical tooth mobility using fixed splints. So it can be a cost and time effective treatment option. In this case, it used a T-Scan System for confirmation a bilateral balanced occlusion and a occlusal force distribution reflected a patient's functional mandibular movement.