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- 저자 : Yang Wanting (검색결과 5 건)
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A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia
Yang, Suk-Kyun,Hong, Myunghee,Baek, Jiwon,Choi, Hyunchul,Zhao, Wanting,Jung, Yusun,Haritunians, Talin,Ye, Byong Duk,Kim, Kyung-Jo,Park, Sang Hyoung,Park, Soo-Kyung,Yang, Dong-Hoon,Dubinsky, Marla,Lee, Nature Pub. Co 2014 Nature genetics Vol.46 No.9
Thiopurine therapy, commonly used in autoimmune conditions, can be complicated by life-threatening leukopenia. This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent. Here we performed an Immunochip-based 2-stage association study in 978 Korean subjects with Crohn's disease treated with thiopurines. We identified a nonsynonymous SNP in NUDT15 (encoding p.Arg139Cys) that was strongly associated with thiopurine-induced early leukopenia (odds ratio (OR) = 35.6; P<SUB>combined</SUB> = 4.88 × 10<SUP>−94</SUP>). In Koreans, this variant demonstrated sensitivity and specificity of 89.4% and 93.2%, respectively, for thiopurine-induced early leukopenia (in comparison to 12.1% and 97.6% for TPMT variants). Although rare, this SNP was also strongly associated with thiopurine-induced leukopenia in subjects with inflammatory bowel disease of European descent (OR = 9.50; P = 4.64 × 10<SUP>−4</SUP>). Thus, NUDT15 is a pharmacogenetic determinant for thiopurine-induced leukopenia in diverse populations.
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Yang, Suk-Kyun,Hong, Myunghee,Zhao, Wanting,Jung, Yusun,Tayebi, Naeimeh,Ye, Byong Duk,Kim, Kyung-Jo,Park, Sang Hyoung,Lee, Inchul,Shin, Hyoung Doo,Cheong, Hyun Sub,Kim, Lyoung Hyo,Kim, Hyo-Jong,Jung, Oxford University Press 2013 Inflammatory bowel diseases Vol.19 No.5
<P>Recent genome-wide association studies and meta-analyses have identified 47 susceptibility loci for ulcerative colitis (UC) in Caucasian populations. A previous genome-wide association study of UC in a Japanese population suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. We performed a genome-wide association studies to identify UC susceptibility loci in a Korean population and further comparative study.</P>
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Yang, Suk-Kyun,Hong, Myunghee,Zhao, Wanting,Jung, Yusun,Baek, Jiwon,Tayebi, Naeimeh,Kim, Kyung Mo,Ye, Byong Duk,Kim, Kyung-Jo,Park, Sang Hyoung,Lee, Inchul,Lee, Eun-Ju,Kim, Won Ho,Cheon, Jae Hee,Kim, BMJ Publishing Group Ltd 2014 Gut Vol.63 No.1
<P><B>Objective</B></P><P>Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations.</P><P><B>Methods</B></P><P>We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls.</P><P><B>Results</B></P><P>We confirmed four previously reported loci: <I>TNFSF15</I>, <I>IL23R</I>, the major histocompatibility complex region, and the <I>RNASET2-FGFR1OP-CCR6</I> region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10<SUP>−14</SUP>), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10<SUP>−10</SUP>) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10<SUP>−9</SUP>), implicating <I>ATG16L2</I> and/or <I>FCHSD2</I> as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of <I>ATG16L2</I> with stronger association (OR=1.61, combined p=2.44×10<SUP>−12</SUP>) than rs11235667, suggesting <I>ATG16L2</I> as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10<SUP>−5</SUP>)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans.</P><P><B>Conclusions</B></P><P>Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.</P>
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Impairment of AMPK-α2 augments detrusor contractions in bladder ischemia
Jing-Hua Yang,Wanting Niu,Yedan Li,Kazem M. Azadzoi 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.5
Purpose: Ischemia disrupts cellular energy homeostasis. Adenosine monophosphate-activated protein kinase alpha-2 (AMPK-α2) is a subunit of AMPK that senses cellular energy deprivation and signals metabolic stress. Our goal was to examine the expression levels and functional role of AMPK-α2 in bladder ischemia. Materials and Methods: Iliac artery atherosclerosis and bladder ischemia were engendered in apolipoprotein E knockout rats by partial arterial endothelial denudation using a balloon catheter. After eight weeks, total and phosphorylated AMPK-α2 expression was analyzed by western blotting. Structural integrity of AMPK-α2 protein was assessed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Functional role of AMPK-α2 was examined by treating animals with the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D ribofuranoside (AICAR). Tissue contractility was measured in the organ bath and bladder nerve density was examined by immunostaining. Results: Total AMPK-α2 expression increased in bladder ischemia, while phosphorylated AMPK-α2 was significantly downregulated. LC-MS/MS suggested post-translational modification of AMPK-α2 functional domains including phosphorylation sites, suggesting accumulation of catalytically inactive AMPK-α2 in bladder ischemia. Treatment of rats with AICAR diminished the force of overactive detrusor contractions and increased bladder capacity but did not have a significant effect on the frequency of bladder contractions. AICAR diminished contractile reactivity of ischemic tissues in the organ bath and prevented loss of nerve fibers in bladder ischemia. Conclusions: Ischemia induces post-translational modification of AMPK-α2 protein. Impairment of AMPK-α2 may contribute to overactive detrusor contractions and loss of nerve fibers in bladder ischemia. AMPK activators may have therapeutic potential against detrusor overactivity and neurodegeneration in bladder conditions involving ischemia.
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Ma Yanyan,Zhang Weida,CHENGSHAOBO,Yang Wanting,Liu Yuxing,Yang Shengyu,Zhang Xinling,Guo Minrui,Chen Guogang 한국원예학회 2022 Horticulture, Environment, and Biotechnology Vol.63 No.6
Prunus domestica L. cv. Ximei fruit perishes quickly due to intense metabolic activity after being harvested. To prolong shelf life and maintain fruit quality, the eff ects of 1-methylcyclopropene (1-MCP) treatment on P. domestica fruit during storage at 4 ± 1 °C were investigated. The results showed that the soluble solid content (SSC), respiratory rate (29.8%), ethylene production (27.2%), anthocyanin content, malonaldehyde content (MDA), hydrogen peroxide content (H 2O2), and superoxide anion activity (O 2·−) of P. domestica fruit were all signifi cantly reduced by 1-MCP treatment (1.0 μL L −1), while the content of ascorbic acid and total phenol, and the activity of SUPEROXIDE DISMUTASE (SOD, 61.3%), CATALASE (CAT, 39.0%), ASCORBATE PEROXIDASE (APX, 23.7%), and PEROXIDASE (POD, 38.0%) increased compared to untreated fruit after 35 days of cold storage. Overall, 1-MCP treatment could maintain high postharvest quality and anti- oxidant activity in P. domestica fruit
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