• 대한임상검사과학회지
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• 제54권4호
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• pp.316-324
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• 2022

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy in women of reproductive age. The genetics of PCOS is heterogeneous with the involvement of number of genes in the steroid synthesis pathway. The CYP11B2 encodes aldosterone synthase and the genetic variants might increase aldosterone secretion in PCOS cases. CYP1A1 is known to enhance the intraovarian catechol estrogen production and thus the propensity for PCOS. The present case-control study analyzed a total of 619 females for CYP11B2 (rs1799998) and CYP1A1 (rs4646903) polymorphisms. Obesity was examined according to body mass index (BMI) and waist hip ratio (WHR) categorization. Biochemical (lipid profile) analysis was performed in PCOS females. BMI (P=0.0001) and WHR (P=0.0001) revealed a statistically significant difference between PCOS cases and controls. The overall levels of triglycerides were higher in PCOS females. The genotype frequency distribution of CYP11B2 (rs1799998) polymorphism revealed statistically significant difference between PCOS cases and controls (P=0.017). However, CYP1A1 (rs4646903) polymorphism did not showed any association with PCOS. The present case-control association analysis is first from our region for CYP1A1 and CYP11B2 polymorphisms and is suggestive of genetic predisposition of steroidogenic genes among PCOS patients in the North-Indian Punjabi females.

• Mycobiology
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• 제48권2호
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• pp.148-152
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• 2020

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.407-412
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• 2001

Many drugs are primarily metabolized by the cytochrome P450s (CYPs). Drug metabolites would be important allergens for adverse drug reactions such as drug eruptions. Skin tests with a suspected drug have conducted to identify causative drugs of drug eruptions, with vehicles such as white petrolatum, DMSO, ethanol. This study will compare the expression of rat CYP isozyme mRNAs between the skin and the liver, with examining an effect of the vehicles on the cutaneous CYPs using semi-quantitative RT-PCR. Thirty-two Sprague-Dawley rats between the ages of six and eight weeks were divided as four groups. One group was used to compare the constitutive mRNA expression between skin and liver, while the others were to examine the effects of three vehicles. The ratios of expression of CYP1A2, CYP2B1/2, CYP2E1, CYP3A1, and CYP4A1 were significantly higher in the liver than the skin. However, CYP1A1 and CYP2C11 were higher in the skin than liver. The effects of vehicles were quite different; white petrolatum significantly induced CYP1A1 (p=0.012) and CYP2C11 mRNAs, while ethanol inhibited CY P1A1 and CYP2B1/2. DMSO did not make any changes. The results suggest that rat skin can participate in drug metabolism with their own CYP isozymes. The effects of vehicles on the cutaneous CYP expression should not be ignored and may be applied for determination of an appropriate vehicle for certain drug(s).

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4583-4587
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• 2015

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

• 환경생물
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• 제26권2호
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• pp.87-93
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• 2008

낙동강 상류로부터 유입되는 각종 오염물질로 심하게 오염된 낙동강 하구역에서 오염정도가 다른 두 지역으로부터 문절망둑 Acanthogobius flavimanus을 채집하여 이들의 간중량지수(HSI), 생식선중량지수(GSI), 해독효소계 및 성 호르몬 수준을 비교하였다. 해독효소계로는 cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), ethokyresorufin deethylase (EROD), glutathione S-transferase (GST)를 조사하였고, 성 호르몬으로는 자성호르몬인 17$\beta$-estradio(E2)을 비롯하여 웅성호르몬인 testosterone (TT), 11-ketotestolterone (11-KT)을 측정하였다. 그 결과, HSI는 site 1에서 잡은 것이 암수 모두 유의적으로 컸고, GSI는 site 1의 암컷에서 유의적으로 작았다. 그리고 성호르몬 중 11-KT과 TT농도는 오염지역에 따라 차이를 보이지 않았지만, E2농도는 site 1에서 유의적으로 높았다(p<0.05).그리고 해독효소계의 수준은 site 1의 것이 CYP와 EROD수준은 유의적으로 낮았던 반면에 P450R, b5R 및 GST 활성은 site 1에서 높았다. 이들 결과를 정리하면, 낙동강 하구에 서식하는 문절망둑은 성 호르몬 대사를 교란시키는 화합물에 의해 영향을 받고 있으며, 특히 암컷이 더욱 크게 받는다는 것을 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3253-3256
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• 2015

Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.223-228
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• 2002

Hypertension is characterized by multiple genetic and environmental factors. To establish the genetic basis of hypertension in Koreans, we investigated the genetic variations of two candidate genes (aldosterone synthase (CYP11B2), ${\gamma}$ subunit of the amiloride-sensitive epithelial sodium channel (ENaC) in the Korean patients with hypertension and normotensive controls. There were no significant differences in the genotype and allele frequencies between two groups, respectively. However, there was the significant difference between Korean and Caucasian populations in allele frequency of RFLPs in the two candidate genes. Therefore, these studies also need to be confirmed in other ethnic groups, although our results do not support a possible role of these genes on hypertension in Korean population

• 생명과학회지
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• 제28권7호
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• pp.835-840
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• 2018

본 연구는 시토크롬 P450 단백질을 암호화하는 애기장대 유래의 AtCYP78A7을 과발현하는 형질전환 식물체로부터 AtCYP78A7 단백질을 특이적으로 인식하는 단일큰론 항체의 제조와 그 항체를 AtCYP78A7 단백질과 접촉시켜 항원-항체 복합체 형성을 검출함으로써 AtCYP78A7 단백질을 효소면역학적(ELISA) 방법으로 검출하는 진단 키트를 개발하기 위하여 수행하였다. 재조합한 GST-AtCYP78A7 단백질을 항원으로 사용하여 단일클론 항체를 분비하는 융합세포주를 제조한 후 비오틴화 및 페어링 테스트를 통해 포획항체와 검출항체를 선정하였으며, GST-AtCYP78A7 정제 단백질을 기준으로 일품벼, 화영벼, AtCYP78A7 과발현 벼(10B-5, 18A-4)의 용해물을 검출항원으로 사용하여 product test를 진행하였다. 그 결과 AtCYP78A7 단백질에 특이적으로 결합하는 4개의 단클론 항체(mAb 6A7, mAb 4C2, mAb 11H6, mAb 7E8)를 생산하였고, 포획항체 mAb 4C2와 검출항체 mAb 7E8-biotin의 조합으로 ELISA 키트를 개발하였다. 개발된 ELISA 키트를 이용한 벼 시료의 분석 결과 AtCYP78A7 과발현 벼는 전체 단백질 대비 AtCYP78A7 단백질의 비율이 0.1% 이상인 양성으로, 일품벼와 화영벼는 0.1% 미만인 음성으로 나타나 키트를 이용한 AtCYP78A7 단백질의 검출이 가능하였으며, 따라서 본 키트는 향후 AtCYP78A7를 과발현하는 형질전환 작물을 대상으로 하는 환경 모니터링 또는 인체 위해성 평가에 유용하게 활용될 수 있을 것으로 사료된다.

• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.257-268
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• 2021

Phthalates and their metabolites are well-known endocrine disrupting chemicals. Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in industry and the exposing possibility to adult is high. In this study, DEHP was treated (133 ㎍/L and 1,330 ㎍/L in drinking water) according to the OECD test guideline 443 to mature female mice and their adrenal gland were examined for histological characteristics and steroidogenic gene expression. The wet weight of the adrenal gland was increased in all administrated groups compared to control. The diameter of zona fasciculata (ZF) was increased by DEHP in both outer ZF and inner ZF but there was no difference in morphology of the cells and arrangements into zona between groups. In addition, the arrangement of extracellular matrix was not different between control and DEHP groups. CYP11B1 was mainly localized at ZF and the intensity was not different between groups. DAX1 was localized in zona glomerulosa (ZG) and ZF, and its expression levels were decreased by DEHP administration. Its level was lower in DEHP133 group than DEHP1330 group. On the other hand, CYP17A1 was localized in ZG of DEHP1330 group. These results suggest that chronic low-dose DEHP exposing may modify the microstructure and function of the adrenal cortical cortex.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.343-347
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• 2006

The present study was designed to investigate the effects renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and local natriuretic peptide (NP) system for glomerulopathy induced in the experimental bilateral ureteral obstructive rats. Sprague-Dawley male rats ($200{\sim}220g$ body weight) were bilaterally obstructed by ligation of the proximal ureters for 24 hours. Control rats were treated in the same ways, except that no ligature was made. The glomeruli were isolated from cortex by graded sieve methods, and the mRNA expressions of local renin-angiotensin system (RAS), aldosterone synthase (CYP11B2), endothelin-1 (ET-1) and NP system were determined by real-time polymerase chain reaction. Following the bilateral ureteral obstruction, the mRNA expressions of renin, angiotensin converting enzyme 1 as well as ET-1 were increased, while that of angiotensin converting enzyme 2 was not changed. The expressions of CYP11B2 and angiotensin II receptors were not changed. C-type natriuretic peptide (CNP) expression was increased, while its receptors (natriuretic peptide receptor-B) were not changed. We suggest that the upregulation of local RAS and ET playa role in the progressive glomerular injury, and that the enhanced CNP activity also plays a compensatory role in obstructive uropathy in the glomerulus.