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8. Immunochip Analysis Identification of 6 Additional Susceptibility Loci for Crohn's Disease in Koreans

Author

Yang, Suk-Kyun, Hong, Myunghee, Choi, Hyunchul, Zhao, Wanting, Jung, Yusun, Haritunians, Talin, Ye, Byong Duk, Kim, Kyung-Jo, Park, Sang Hyoung, Lee, Inchul, Kim, Won Ho, Cheon, Jae Hee, Kim, Young-Ho, Jang, Byung Ik, Kim, Hyun-Soo, Choi, Jai Hyun, Koo, Ja Seol, Lee, Ji Hyun, Jung, Sung-Ae, Shin, Hyoung Doo, Kang, Daehee, Youn, Hee-Shang, Taylor, Kent D, Rotter, Jerome I, Liu, Jianjun, McGovern, Dermot PB, and Song, Kyuyoung

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Inflammatory Bowel Disease, Human Genome, Autoimmune Disease, Crohn's Disease, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Asian People, Biomarkers, Case-Control Studies, Cohort Studies, Crohn Disease, Female, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Odds Ratio, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Prognosis, Young Adult, Crohn's disease, genetics, ImmunoChip, Korean, Gastroenterology & Hepatology, Clinical sciences
Abstract

BackgroundCrohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population.MethodsUsing the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls.ResultsWe confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans.ConclusionsAlthough the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

Published
2015

10. A genome-wide association study identifies potential susceptibility loci for Hirschsprung disease.

Author

Kim, Jeong-Hyun, Cheong, Hyun Sub, Sul, Jae Hoon, Seo, Jeong-Meen, Kim, Dae-Yeon, Oh, Jung-Tak, Park, Kwi-Won, Kim, Hyun-Young, Jung, Soo-Min, Jung, Kyuwhan, Cho, Min Jeng, Bae, Joon Seol, and Shin, Hyoung Doo

Subjects
Chromosomes, Human, Humans, Hirschsprung Disease, Genetic Predisposition to Disease, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Female, Male, Genome-Wide Association Study, Genetic Loci, Chromosomes, Human, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of intramural nervous plexuses along variable lengths of the hindgut. Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus. To discover additional risk loci, we performed a GWAS of 123 sporadic HSCR patients and 432 unaffected controls using a large-scale platform with coverage of over 1 million polymorphic markers. The result was that our study replicated the findings of RET-CSGALNACT2-RASGEF1A genomic region (rawP = 5.69×10(-19) before a Bonferroni correction; corrP = 4.31×10(-13) after a Bonferroni correction) and NRG1 as susceptibility loci. In addition, this study identified SLC6A20 (adjP = 2.71×10(-6)), RORA (adjP = 1.26×10(-5)), and ABCC9 (adjP = 1.86×10(-5)) as new potential susceptibility loci under adjusting the already known loci on the RET-CSGALNACT2-RASGEF1A and NRG1 regions, although none of the SNPs in these genes passed the Bonferroni correction. In further subgroup analysis, the RET-CSGALNACT2-RASGEF1A genomic region was observed to have different significance levels among subgroups: short-segment (S-HSCR, corrP = 1.71×10(-5)), long-segment (L-HSCR, corrP = 6.66×10(-4)), and total colonic aganglionosis (TCA, corrP>0.05). This differential pattern in the significance level suggests that other genomic loci or mechanisms may affect the length of aganglionosis in HSCR subgroups during enteric nervous system (ENS) development. Although functional evaluations are needed, our findings might facilitate improved understanding of the mechanisms of HSCR pathogenesis.

Published
2014

38. Association Analysis of Melanocortin 3 Receptor Polymorphisms with the Risk of Pulmonary Tuberculosis

Author

Park, Byung Lae, Kim, Lyoung Hyo, Namgoong, Suhg, Kim, Ji On, Kim, Jason Yongha, Chang, Hun Soo, Park, Jong Sook, Jang, An Soo, Park, Sung Woo, Kim, Do Jin, Kim, Ki Up, Kim, Yang Gee, Uh, Soo-Taek, Seo, Ki Hyun, Kim, Young Hoon, Park, Choon Sik, and Shin, Hyoung Doo

Subjects
Twins -- Research -- Health aspects, Genetic polymorphisms -- Research, Tuberculosis -- Research -- Risk factors -- Patient outcomes -- Development and progression -- Care and treatment, Health
Abstract

Purpose Melanocortin 3 Receptor (MC3R) is one of the families of seven-transmembrane G-protein-coupled receptors, and a recent study showed that MCR3 promoter polymorphism was significantly associated with the susceptibility of tuberculosis (TB) in South African population. Methods We analyzed six MC3R polymorphisms to examine the genetic effects on the risk of pulmonary TB in Korean subjects by using TaqMan assays and case-control analyses. Results Using statistical analyses, one common promoter polymorphism (MC3Rrs11575886 T > C) was found to be associated with an increased risk of pulmonary TB. The frequency of the C-bearing genotype of rs11575886 was higher in pulmonary TB patients than in normal controls (p = 0.03, OR = 1.46) although the significance was not retained after correction. In silico analysis for the difference of transcription binding factor (TF), motif between C and T allele demonstrated that the TF motif and its threshold scores of C allele were lower than those of T allele. Conclusions The C allele of rs11575886 could be a risk allele for the pulmonary TB by affecting the binding of TF. Our findings suggest that polymorphisms in MC3R might be one of genetic factors for the risk of pulmonary TB development in Korean subjects. Electronic supplementary material The online version of this article (doi:10.1007/s00408-014-9625-2) contains supplementary material, which is available to authorized users., Author(s): Byung Lae Park[sup.1] , Lyoung Hyo Kim[sup.1] [sup.2] , Suhg Namgoong[sup.1] [sup.2] , Ji On Kim[sup.1] [sup.2] , Jason Yongha Kim[sup.2] , Hun Soo Chang[sup.3] [sup.4] [sup.5] , Jong [...]

Published
2014
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39. ADAM33 Gene Polymorphisms are Associated with the Risk of Idiopathic Pulmonary Fibrosis

Author

Uh, Soo-Taek, Jang, An-Soo, Park, Sung-Woo, Park, Jong-Sook, Min, Chang-Gi, Kim, Yong Hoon, Park, Byung-Lae, Shin, Hyoung Doo, Kim, Dong Soon, and Park, Choon-Sik

Subjects
Pulmonary fibrosis -- Research -- Care and treatment -- Genetic aspects -- Development and progression, Genetic polymorphisms -- Research, Health
Abstract

Background Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function due to remodeling of the lung, including epithelial mesenchymal transition. ADAM33 is a disintegrin and metalloprotease domain-containing protein, which may be related to lung fibrosis by exerting angiogenesis and remodeling of the lung. Thus, we evaluated the association of single-nucleotide polymorphisms (SNPs) of ADAM33 with the risk of IPF. Methods A total of 237 patients with IPF and 183 healthy subjects participated in the present study. Nine polymorphisms were selected. Genotyping was performed by single-base extension. Polymorphisms and haplotypes were analyzed for associations with the risk of IPF using multiple logistic regression models controlling for age, gender, and smoking status as covariates. Results All SNPs were in Hardy-Weinberg equilibrium. The minor allele frequency (MAF) of rs628977G>A in intron 21 was significantly lower in subjects with surgical IPF than in normal controls in the recessive model [33.2 vs. 38.0 %, p = 0.02, OR = 0.40 (0.19-0.84)]. When the subjects with clinical IPF were included, the difference in MAF persisted with a p value of 0.03 [OR = 0.50 (0.27-0.94)]. Conclusions ADAM33 rs628977G>A was marginally associated with a decreased risk of IPF in a recessive model., Author(s): Soo-Taek Uh[sup.1] , An-Soo Jang[sup.2] , Sung-Woo Park[sup.2] , Jong-Sook Park[sup.2] , Chang-Gi Min[sup.2] , Yong Hoon Kim[sup.3] , Byung-Lae Park[sup.4] , Hyoung Doo Shin[sup.4] [sup.5] , Dong Soon [...]

Published
2014
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41. List of Contributors

Author

Abadie-Guedes, Ricardo, primary, Abi-Dargham, Anissa, additional, Abulseoud, Osama A., additional, Acevska, Jelena, additional, Adan, Ana, additional, Aguilar, María A., additional, Akhgari, Maryam, additional, Ali, Robert, additional, Anderson-Mooney, Amelia J., additional, Anees, Muhammad, additional, Arenas, M. Carmen, additional, Arndt, Jamie, additional, Ascheri, Daniele, additional, Ashraf, Nida, additional, Ashton, Maxie, additional, Asimaki, Olga, additional, Aubry, Jean-Michel, additional, Aujla, Harinder, additional, Awad, A. George, additional, Awara, Mahmoud A., additional, Bagues, Ana, additional, Balhara, Yatan P.S., additional, Bambico, Francis, additional, Barrio-Real, Laura, additional, Bartlett, Selena E., additional, Basavarajappa, Balapal S., additional, Basu, Aniruddha, additional, Bau, Claiton H.D., additional, Beattie, Matthew C., additional, Becker, Benjamin, additional, Beer, Anton L., additional, Behera, Deepak, additional, Benaiges, Irina, additional, Bergen-Cico, Dessa, additional, Bergeson, Susan E., additional, Berrettini, Wade H., additional, Bertoglio, Leandro J., additional, Bockman, Charles S., additional, Borgwardt, Stefan, additional, Bourque, Josiane, additional, Bozkurt, Muge, additional, Brennan, Katharine Alexandra, additional, Briggs, Hilary, additional, Brooks, Samanth J., additional, Bulcão, Rachel Picada, additional, Burkhardt, Ute, additional, Butler, Tracy R., additional, Cabrera, Eduardo Rodrigues, additional, Caldirola, Daniela, additional, Callaghan, Russell C., additional, Callegari, Elza, additional, Caloca, María J., additional, Campos, Alline C., additional, Cannizzaro, Carla, additional, Cape, Gavin, additional, Carnell, Benjamin L., additional, Caso, Javier R., additional, Cendron, Lucas Henrique, additional, Chang, Yun-Hsuan, additional, Cheng, Gordon L.F., additional, Chen, Kao Chin, additional, Chopra, Kanwaljit, additional, Chow, Tony C.H., additional, Cico, Rachael, additional, Cook, Jason B., additional, Coppola, Maurizio, additional, Cortes-Briones, Jose A., additional, Cousijn, Janna, additional, Crist, Richard C., additional, Crocker, Candice E., additional, Danielson, Kirsty, additional, Dasilva, Miguel, additional, Dave, Malay, additional, De Biasi, Mariella, additional, de Carvalho, Cristiane R., additional, De Guio, François, additional, De Ridder, Dirk, additional, Dhiman, Sonia, additional, Diaferia, Giuseppina, additional, Diana, Marco, additional, DiFranza, Joseph R., additional, Dimitrovska, Aneta, additional, Dinh-Williams, Le-Anh, additional, Djurendic-Brenesel, Maja, additional, Dodd, Jonathan N., additional, Dodge, Neil C., additional, Drew, Paul D., additional, Drucker Colín, Rene, additional, Dujmovic, Irena, additional, Dutra Arbo, Marcelo, additional, Edwards, Scott, additional, Etemadi-Aleagha, Afshar, additional, Evren, Cuneyt, additional, Fang, Juan, additional, Fernández-Rodríguez, Camino, additional, Filipovic, Radmila, additional, Finsterer, Josef, additional, Fitzgerald, Megan L., additional, Fogaça, Manoela V., additional, Forero, Diego A., additional, Fouad Moselhy, Hamdy, additional, Freitas, Marco Antonio de, additional, Galletly, Cherrie, additional, García-Bueno, Borja, additional, Gatley, Jodi M., additional, Germanaud, David, additional, Gifford, Roger S., additional, Glue, Paul, additional, Gobbi, Gabriella, additional, Goicoechea, Carlos, additional, González-Arnay, Emilio, additional, González-Reimers, Emilio, additional, González-Sarmiento, Rogelio, additional, Gowing, Linda, additional, Grieve, Kenneth L., additional, Guedes, Rubem Carlos Araújo, additional, Guerri, Consuelo, additional, Guimarães, Francisco S., additional, Guller, Leila, additional, Harland, Jennifer, additional, Hashemi, Seyyed A., additional, Hashemizadeh, Shiva, additional, He, Bei, additional, Hernández-López, Salvador, additional, Hickle, Tyson, additional, Hill, Shirley Y., additional, Holgate, Joan, additional, Huang, Wei, additional, Huang, Wei-Lieh, additional, Hunt, Nicholas J., additional, Hurlemann, René, additional, Iannone, Giuseppe, additional, Idrees, Fariha, additional, Idrees, Jawaria, additional, Ikeda, Kazutaka, additional, Ivanashvili, Nato, additional, Ivanov, Iliyan, additional, Jacobson, Joseph L., additional, Jacobson, Sandra W., additional, Järbe, Torbjörn U.C., additional, Jiang, Y.L., additional, Jokar, Farzaneh, additional, Kane, Cynthia J.M., additional, Kangiser, Megan, additional, Karpyak, Victor, additional, King, Jean A., additional, Kivell, Bronwyn M., additional, Kiyatkin, Eugene A., additional, Klein, Jochen, additional, Klima, Michelle L., additional, Kodirov, Sodikdjon A., additional, Korostynski, Michal, additional, Kreek, Mary Jeanne, additional, Kulevanova, Svetlana, additional, Kumar, Santosh, additional, Langguth, Berthold, additional, Leal, Mirna Bainy, additional, Lee, Sheng-Yu, additional, Lee, Tatia M.C., additional, Leikaif, John, additional, Lin, Shih-Hsien, additional, Lin, Yu-Hsuan, additional, Liu, Xiu, additional, Lorenzetti, Valentina, additional, Lu, Ru-Band, additional, Machaalani, Rita, additional, Maldonado-Devincci, Antoniette, additional, Mangin, Jean-François, additional, Mangoura, Dimitra, additional, Manning, Patrick, additional, Marcu, Jahan P., additional, McCabe, Simon, additional, McGinn, M. Adrienne, additional, McKinney, Diana L., additional, McLaughin, Ryan, additional, McLaughlin, Ian, additional, Meintjes, Ernesta, additional, Midde, Narasimha M., additional, Mihailescu, Stefan, additional, Miñarro, José, additional, Mondola, Raffaella, additional, Leslie Morrow, A., additional, Mota, Nina R., additional, Newcorn, Jeffrey, additional, Nishizawa, Daisuke, additional, Nobrega, José N., additional, Nona, Christina N., additional, Nuñez, Nicolas, additional, Nylander, Ingrid, additional, O’Brien, Jessica W., additional, Oliva, Francesco, additional, Palm, Sara, additional, Papini, Mauricio R., additional, Park, Byung Lae, additional, Pascual, María, additional, Pedraza, Juan, additional, Perna, Giampaolo, additional, Picci, Rocco Luigi, additional, Piechota, Marcin, additional, Pilija, Vladimir, additional, Pinto, Charles, additional, Potvin, Stéphane, additional, Prasad Rawat, Jagdeo, additional, Preedy, Victor R., additional, Priddy, Brittany M., additional, Przewlocki, Ryszard, additional, Raghav, Jimit G., additional, Rajendram, Rajkumar, additional, Rajendram, Roshanna, additional, Rao, P.S.S., additional, Ray, Anirban, additional, Rezayof, Ameneh, additional, Rivadulla, Casto, additional, Rodríguez-Arias, Marta, additional, Rossato, Luciana Grazziotin, additional, Rovaris, Diego L., additional, Ruby, Christina L., additional, Sakellaridis, Nikos, additional, Salman, Saad, additional, Santolaria-Fernández, Francisco, additional, Sarkar, Siddharth, additional, Schechter, Jason B., additional, Schmidt, André, additional, Scholl, Susan, additional, Scott, April, additional, Shariff, Masroor, additional, Sharma, Shiwali, additional, Shin, Hyoung Doo, additional, Singh, Thakur Gurjeet, additional, Sinha, Namita, additional, Skosnik, Patrick D., additional, Bezerra, Ranilson de Souza, additional, Stairs, Dustin J., additional, Stefkov, Gjoshe, additional, Stein, Dan J., additional, Stern, Cristina A.J., additional, Stöllberger, Claudia, additional, Takahashi, Reinaldo N., additional, Tang, H.C., additional, Tarren, Josephine, additional, Tibbo, Philip G., additional, Tiwari, Vinod, additional, Torres, Carmen, additional, Trivelli, Federica, additional, Truman, Penelope, additional, Tsirimonaki, Emmanouella, additional, Vanneste, Sven, additional, Vansickel, Andrea R., additional, Vendruscolo, Leandro F., additional, Wai, Maria S.M., additional, Walter, Marc, additional, Waters, Karen A., additional, Weiner, Jeffrey L., additional, Weinstein, Jodi J., additional, Weisberg, Jordyn, additional, Whitaker, Annie M., additional, Wolf-Stanton, Sarah, additional, Wu, Chen-Ying, additional, Wu, Sharon L., additional, Yang, Cheryl C.H., additional, Yang, Yen Kuang, additional, Yeshwant Tandel, Kirti, additional, Yew, D.T., additional, Yousefzadeh Fard, Yashar, additional, and Zhou, Yan, additional

Published
2016
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49. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci

Author

Kim, Kwangwoo, Bang, So-Young, Lee, Hye-Soon, Cho, Soo-Kyung, Choi, Chan-Bum, Sung, Yoon-Kyoung, Kim, Tae-Hwan, Jun, Jae-Bum, Yoo, Dae Hyun, Kang, Young Mo, Kim, Seong-Kyu, Suh, Chang-Hee, Shim, Seung-Cheol, Lee, Shin-Seok, Lee, Jisoo, Chung, Won Tae, Choe, Jung-Yoon, Shin, Hyoung Doo, Lee, Jong-Young, Han, Bok-Ghee, Nath, Swapan K, Eyre, Steve, Bowes, John, Pappas, Dimitrios A, Kremer, Joel M, Gonzalez-Gay, Miguel A, Rodriguez-Rodriguez, Luis, Ärlestig, Lisbeth, Okada, Yukinori, Diogo, Dorothée, Liao, Katherine P, Karlson, Elizabeth W, Raychaudhuri, Soumya, Rantapää-Dahlqvist, Solbritt, Martin, Javier, Klareskog, Lars, Padyukov, Leonid, Gregersen, Peter K, Worthington, Jane, Greenberg, Jeffrey D, Plenge, Robert M, and Bae, Sang-Cheol

Published
2015
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50. Association of IL-17RB Gene Polymorphism With Asthma

Author

Jung, Ji-Sun, Park, Byung Lae, Cheong, Hyun Sub, Bae, Joon Seol, Kim, Ji-Hye, Chang, Hun Soo, Rhim, TaiYoun, Park, Jong-Sook, Jang, An-Soo, Lee, Young-Mok, Kim, Ki-Up, Uh, Soo-Taek, Na, Ju Ock, Kim, Yong-Hoon, Park, Choon-Sik, and Shin, Hyoung Doo

Published
2009
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