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No Association of the rs17822931 Polymorphism in ABCC11 with Breast Cancer Risk in Koreans
Na, Ann-Yae,Heo, Jin-Chul,Sung, Jin Young,Lee, Jong-Ha,Kim, Yoon-Nyun,Kim, Dae-Kwang Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5
ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (${\Delta}27$) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and ${\Delta}27$ was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans.
Ann-Yae Na,Eun-Ju Yang,Ju Mi Jeon,Sung Hwan Ki,Kyung-Sik Song,Sangkyu Lee 한국독성학회 2018 Toxicological Research Vol.34 No.1
Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL (0~50 μM) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha (PPARα) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanolinduced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and 50 μM of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.
Reevaluation of Single Nucleotide Polymorphism of OCA2 in Koreans
Ann-Yae Na(나안예),Dae-Kwang Kim(김대광) 대한체질인류학회 2016 대한체질인류학회지 Vol.29 No.3
눈피부 백색증 (Oculocutaneous albinism, OCA)은 멜라닌 색소 합성과정의 장애로 피부나 모발, 안구 등 전신에 무색소 또는 저색소증이 나타나는 보통염색체 열성의 이질 유전질환 (heterogenous hereditary disorder)이다. 본 연구는 한국인 250명을 대상으로 OCA2 유전자에 위치한 3개의 단일뉴클레오티드다형태 (Single Nucleotide Polymorphism, SNP)의 분포를 조사하였다. 정상인 DNA를 이용하여 중합효소연쇄반응과 DNA 염기서열분석을 통하여 한국인의 OCA2 단일뉴클레오티드다형태의 분포를 확인하였다. OCA2 유전자 가운데 단일뉴클레오티드다형태는 동아시아 인구 및 아프리카와 유럽의 인구 사이에 30%의 빈도를 차지하는 것을 기준하여 한국인의 단일뉴클레오티드다형태의 분포와 지역적인 차이를 비교하였다. 한국인에서 OCA2 유전자에서 rs1800414과 rs74653330 그리고 rs7497270의 작은대립유전자빈도 (Minor allele frequency, MAF)는 각각 A 대립유전자 38.8%, A 대립유전자 0.8% 그리고 C 대립유전자 33.4%로 나타났다. 이 연구 결과는 유럽인과 백인의 빈도와 다르지만 동아시아인에서는 비슷하였다. 국내 OCA2의 단일뉴클레오티드다형태에 관련된 유전적 정보가 미비하기에, 한국인에 초점을 맞춘 추후 연구가 세계적인 유전적 정보를 확립하기 위해 유용한 연구가 될 것이다. Oculocutaneous albinism type 2 (OCA2) is an autosomal recessive disorder that results from mutations in the P gene, and has approximately 70% function of melanin biosynthesis in the melanocytes. While the overwhelming majority of pigmentation studies have focused on European populations, very little is known about the gene and mechanisms affecting skin lightening in Asian population. The main goal of the study was to test the distribution of three polymorphisms located in a pigmentation candidate gene, OCA2, in a sample of individuals of Koreans (N=250). The genetic markers were selected for polymorphisms that had an allele frequency difference of at least 30% between East Asian populations and European populations. We investigated Minor Allele Frequencies (MAFs) for each of three polymorphisms within OCA2 and reevaluated the difference of the allele frequency along with populations. MAFs of polymorphisms of OCA2 were presented the different frequency in Korean samples (SNP rs1800414 (His615Arg), A allele=38.8%, rs74653330 (Ala481Thr), A allele=0.8% and rs7497270 (intronic polymorphism), C allele=33.4%). While our results had different distributions to European and Caucasians, they showed similar frequencies with East Asian. This study was to reevaluate the distribution of pigmentation candidate gene in Korean samples, further domestic study will aid in developments of the genetic information on worldwide study.
Na, Ann-Yae,Jo, Jung Jae,Kwon, Oh Kwang,Shrestha, Riya,Cho, Pil Joung,Kim, Kyu Min,Ki, Sung Hwan,Lee, Tae Hee,Jeon, Tae Won,Jeong, Tae Cheon,Lee, Sangkyu Elsevier 2018 Toxicology and applied pharmacology Vol.352 No.-
<P><B>Abstract</B></P> <P>Non-alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non-alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well-established, NAFLD-induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD-induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine-choline deficient (MCD) diet to induce development of NAFLD, tandem mass tags-based liquid chromatography-tandem mass spectrometry analysis was conducted to investigate the dynamics of hepatic proteins. A total of 1295 proteins were identified, of which 934 were quantified by proteomic analysis. Among these proteins, 21 proteins were up-regulated and 51 proteins were down-regulated by the MCD diet. Notably, domain annotation enrichment using InterPro indicated that proteins related to CYPs were significantly decreased. When we investigated CYP activity using <I>in vivo</I> and <I>in vitro</I> CYP cocktail assays, most CYPs were significantly decreased, whereas CYP2D was not changed after administration of the MCD diet. In conclusion, we identified significantly altered levels of CYPs and their activities induced by the MCD diet and confirmed the NAFLD-induced drug metabolism by pharmacokinetic analysis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> NAFLD-induced drug metabolism was investigated by comparative toxicoproteomics. </LI> <LI> Among 934 quantified proteins, 21 were up-regulated, and 51 were down-regulated. </LI> <LI> Domain annotation enrichment indicated CYPs were significantly decreased. </LI> <LI> The decreased CYP activities were confirmed by <I>in vivo</I> and <I>in vitro</I> assays. </LI> <LI> Our data provides understanding of the drug-interaction in NAFLD patients. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>