Personalized management of asthma exacerbations: lessons from genetic studies

被引:6
作者
Wang, Alberta L. [1 ,2 ]
Tantisira, Kelan G. [1 ,3 ]
机构
[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA USA
[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA USA
[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA USA
来源
EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT | 2016年 / 1卷 / 06期
基金
美国国家卫生研究院;
关键词
Asthma; gene environment interaction; pharmacogenomics; genome wide association study; candidate gene association study;
D O I
10.1080/23808993.2016.1269600
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The genetics of severe asthma and asthma exacerbations are distinct from milder forms of asthma. Gene-environmental interactions contribute to the complexity and heterogeneity of severe asthma and asthma exacerbations, and pharmacogenomic studies have also identified genes that affect susceptibility to asthma exacerbations. Areas covered: Studies on the genetics, gene-environment interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple individual genetic variants have been identified to be associated with asthma exacerbations but each genetic polymorphism explains only a fraction of the disease and by itself is not able to translate into clinical practice. Research is shifting from candidate gene studies and genome wide association studies towards more integrative approaches to translate genetic findings into clinical diagnostic and therapeutic tools. Expert commentary: Integrative approaches combining polygenic or genomic data with multi-omics technologies have the potential to discover new biologic mechanisms and biomarkers for severe asthma and asthma exacerbations. Greater understanding of genomics and underlying biologic pathways will also lead to improved prevention and treatment, lowering costs, morbidity, and mortality. The utilization of genomic testing and personalized medicine may revolutionize asthma management, in particular for patients with severe, refractory asthma.
引用
收藏
页码:487 / 495
页数:9
相关论文
共 78 条
  • [1] Semaphorin 3d and Semaphorin 3e Direct Endothelial Motility through Distinct Molecular Signaling Pathways
    Aghajanian, Haig
    Choi, Connie
    Ho, Vivienne C.
    Gupta, Mudit
    Singh, Manvendra K.
    Epstein, Jonathan A.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (26) : 17971 - 17979
  • [2] Effect of β2-adrenergic receptor gene (ADRB2) 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response
    Ambrose, Helen J.
    Lawrance, Rachael M.
    Cresswell, Carl J.
    Goldman, Mitchell
    Meyers, Deborah A.
    Bleecker, Eugene R.
    [J]. RESPIRATORY RESEARCH, 2012, 13
  • [3] Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease
    Anderson, Gary P.
    [J]. LANCET, 2008, 372 (9643) : 1107 - 1119
  • [4] Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes
    Baines, Katherine J.
    Simpson, Jodie L.
    Wood, Lisa G.
    Scott, Rodney J.
    Fibbens, Naomi L.
    Powell, Heather
    Cowan, Douglas C.
    Taylor, D. Robin
    Cowan, Jan O.
    Gibson, Peter G.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 133 (04) : 997 - 1007
  • [5] Pathways Activated during Human Asthma Exacerbation as Revealed by Gene Expression Patterns in Blood
    Bjornsdottir, Unnur S.
    Holgate, Stephen T.
    Reddy, Padmalatha S.
    Hill, Andrew A.
    McKee, Charlotte M.
    Csimma, Cristina I.
    Weaver, Amy A.
    Legault, Holly M.
    Small, Clayton G.
    Ramsey, Renee C.
    Ellis, Debra K.
    Burke, Conor M.
    Thompson, Philip J.
    Howarth, Peter H.
    Wardlaw, Andrew J.
    Bardin, Phillip G.
    Bernstein, David I.
    Irving, Louis B.
    Chupp, Geoffrey L.
    Bensch, George W.
    Bensch, Gregory W.
    Stahlman, Jon E.
    Karetzky, Monroe
    Baker, James W.
    Miller, Rachel L.
    Goodman, Brad H.
    Raible, Donald G.
    Goldman, Samuel J.
    Miller, Douglas K.
    Ryan, John L.
    Dorner, Andrew J.
    Immermann, Frederick W.
    O'Toole, Margot
    [J]. PLOS ONE, 2011, 6 (07):
  • [6] Effect of ADRB2 polymorphisms on response to longacting β2-agonist therapy:: a pharmacogenetic analysis of two randomised studies
    Bleecker, Eugene R.
    Postma, Dirkje S.
    Lawrance, Rachael M.
    Meyers, Deborah A.
    Ambrose, Helen J.
    Goldman, Mitch
    [J]. LANCET, 2007, 370 (9605) : 2118 - 2125
  • [7] Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication
    Bochkov, Yury A.
    Watters, Kelly
    Ashraf, Shamaila
    Griggs, Theodor F.
    Devries, Mark K.
    Jackson, Daniel J.
    Palmenberg, Ann C.
    Gern, James E.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (17) : 5485 - 5490
  • [8] A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
    Bonnelykke, Klaus
    Sleiman, Patrick
    Nielsen, Kasper
    Kreiner-Moller, Eskil
    Mercader, Josep M.
    Belgrave, Danielle
    den Dekker, Herman T.
    Husby, Anders
    Sevelsted, Astrid
    Faura-Tellez, Grissel
    Mortensen, Li Juel
    Paternoster, Lavinia
    Flaaten, Richard
    Molgaard, Anne
    Smart, David E.
    Thomsen, Philip F.
    Rasmussen, Morten A.
    Bonas-Guarch, Silvia
    Holst, Claus
    Nohr, Ellen A.
    Yadav, Rachita
    March, Michael E.
    Blicher, Thomas
    Lackie, Peter M.
    Jaddoe, Vincent W. V.
    Simpson, Angela
    Holloway, John W.
    Duijts, Liesbeth
    Custovic, Adnan
    Davies, Donna E.
    Torrents, David
    Gupta, Ramneek
    Hollegaard, Mads V.
    Hougaard, David M.
    Hakonarson, Hakon
    Bisgaard, Hans
    [J]. NATURE GENETICS, 2014, 46 (01) : 51 - +
  • [9] Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure
    Bukvic, Blazenka Kljaic
    Blekic, Mario
    Simpson, Angela
    Marinho, Susana
    Curtin, John A.
    Hankinson, Jenny
    Aberle, Neda
    Custovic, Adnan
    [J]. PEDIATRIC ALLERGY AND IMMUNOLOGY, 2013, 24 (01) : 10 - 18
  • [10] Association between a sequence variant in the IL-4 gene promoter and FEV1 in asthma
    Burchard, EG
    Silverman, EK
    Rosenwasser, LJ
    Borish, L
    Yandava, C
    Pillari, A
    Weiss, ST
    Hasday, J
    Lilly, CM
    Ford, JG
    Drazen, JM
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1999, 160 (03) : 919 - 922