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      KCI등재 SCI SCIE SCOPUS

      Association between Genetic Variations of MERTK and Chronic Obstructive Pulmonary Disease in Koreans

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      https://www.riss.kr/link?id=A105095541

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      다국어 초록 (Multilingual Abstract)

      Background: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans.
      Methods: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays.
      Results: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK.
      Conclusion: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.
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      Background: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regar...

      Background: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans.
      Methods: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays.
      Results: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK.
      Conclusion: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.

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      참고문헌 (Reference)

      1 Choi JY, "Upregulation of Mer receptor tyrosine kinase signaling attenuated lipopolysaccharide-induced lung inflammation" 344 (344): 447-458, 2013

      2 Grabiec AM, "The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation" 38 (38): 409-423, 2016

      3 Bauer CM, "The influence of cigarette smoking on viral infections: translating bench science to impact COPD pathogenesis and acute exacerbations of COPD clinically" 143 (143): 196-206, 2013

      4 Fariz Nurwidya, "The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease" 대한결핵및호흡기학회 79 (79): 5-13, 2016

      5 Rothlin CV, "TAM receptors are pleiotropic inhibitors of the innate immune response" 131 (131): 1124-1136, 2007

      6 Rothlin CV, "TAM receptor signaling in immune homeostasis" 33 (33): 355-391, 2015

      7 Hodge S, "Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease" 37 (37): 748-755, 2007

      8 차승익, "SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease" 대한의학회 24 (24): 1119-1125, 2009

      9 Thompson DA, "Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively" 70 (70): 224-229, 2002

      10 Koutroubakis IE, "Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease" 95 (95): 190-194, 2000

      1 Choi JY, "Upregulation of Mer receptor tyrosine kinase signaling attenuated lipopolysaccharide-induced lung inflammation" 344 (344): 447-458, 2013

      2 Grabiec AM, "The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation" 38 (38): 409-423, 2016

      3 Bauer CM, "The influence of cigarette smoking on viral infections: translating bench science to impact COPD pathogenesis and acute exacerbations of COPD clinically" 143 (143): 196-206, 2013

      4 Fariz Nurwidya, "The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease" 대한결핵및호흡기학회 79 (79): 5-13, 2016

      5 Rothlin CV, "TAM receptors are pleiotropic inhibitors of the innate immune response" 131 (131): 1124-1136, 2007

      6 Rothlin CV, "TAM receptor signaling in immune homeostasis" 33 (33): 355-391, 2015

      7 Hodge S, "Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease" 37 (37): 748-755, 2007

      8 차승익, "SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease" 대한의학회 24 (24): 1119-1125, 2009

      9 Thompson DA, "Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively" 70 (70): 224-229, 2002

      10 Koutroubakis IE, "Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease" 95 (95): 190-194, 2000

      11 Ma GZ, "Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with multiple sclerosis susceptibility" 6 (6): e16964-, 2011

      12 Lee SY, "Polymorphisms in matrix metalloproteinase-1, -9 and -12 genes and the risk of chronic obstructive pulmonary disease in a Korean population" 80 (80): 133-138, 2010

      13 Lee JM, "Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case-control study" 102 (102): 1311-1320, 2008

      14 Gautherot J, "Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations" 60 (60): 610-621, 2014

      15 Scott RS, "Phagocytosis and clearance of apoptotic cells is mediated by MER" 411 (411): 207-211, 2001

      16 Kazeros A, "Overexpression of apoptotic cell removal receptor MERTK in alveolar macrophages of cigarette smokers" 39 (39): 747-757, 2008

      17 Cakal B, "Natural anticoagulant protein levels in Turkish patients with inflammatory bowel disease" 21 (21): 118-121, 2010

      18 Gal A, "Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa" 26 (26): 270-271, 2000

      19 Schlegel J, "MERTK receptor tyrosine kinase is a therapeutic target in melanoma" 123 (123): 2257-2267, 2013

      20 Keating AK, "Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase" 25 (25): 6092-6100, 2006

      21 Lee YJ, "Inhibiting Mer receptor tyrosine kinase suppresses STAT1, SOCS1/3, and NF-${\kappa}B$ activation and enhances inflammatory responses in lipopolysaccharide-induced acute lung injury" 91 (91): 921-932, 2012

      22 Holloway RA, "Immunopathogenesis of chronic obstructive pulmonary disease" 19 (19): 95-102, 2013

      23 Zhou X, "Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP" 21 (21): 1325-1335, 2012

      24 Chen J, "Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation" 14 (14): 2033-2039, 1997

      25 Liu G, "High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine" 181 (181): 4240-4246, 2008

      26 Pauwels RA, "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary" 163 (163): 1256-1276, 2001

      27 Hancock DB, "Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function" 8 (8): e1003098-, 2012

      28 Wilk JB, "Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction" 186 (186): 622-632, 2012

      29 Kim DK, "Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease" 186 (186): 1238-1247, 2012

      30 International Multiple Sclerosis Genetics ConsortiumWellcome Trust Case Control Consortium 2Sawcer S, "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis" 476 (476): 214-219, 2011

      31 Busch R, "Genetic association and risk scores in a chronic obstructive pulmonary disease meta-analysis of 16,707 subjects" 57 (57): 35-46, 2017

      32 Soler Artigas M, "Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function" 184 (184): 786-795, 2011

      33 Zagorska A, "Diversification of TAM receptor tyrosine kinase function" 15 (15): 920-928, 2014

      34 Cohen PL, "Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase" 196 (196): 135-140, 2002

      35 Hodge S, "Cigarette smoke-induced changes to alveolar macrophage phenotype and function are improved by treatment with procysteine" 44 (44): 673-681, 2011

      36 Di Marco F, "Chronic obstructive pulmonary disease diagnosis: the simpler the better? Not always" 24 (24): 199-202, 2013

      37 Johannessen CM, "COT drives resistance to RAF inhibition through MAP kinase pathway reactivation" 468 (468): 968-972, 2010

      38 Kim WJ, "Association of lung function genes with chronic obstructive pulmonary disease" 192 (192): 473-480, 2014

      39 Hodge S, "Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells" 81 (81): 289-296, 2003

      40 Cho MH, "A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13" 21 (21): 947-957, 2012

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2005-01-01 평가 SCI 등재 (등재유지) KCI등재
      2002-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      1999-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 1.48 0.37 1.06
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.85 0.75 0.691 0.11
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