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• W2016457422 abstract "Genetic studies have indicated a role for variability of genes in the leukotriene pathway in disease susceptibility and medication response. Although the studies to date have been generally limited by small sample sizes and a lack of independent replication, multiple loci within multiple genes have now been associated with more than 1 association related to asthma or asthma treatment response (Table I).5Kedda M.A. Shi J. Duffy D. Phelps S. Yang I. O'Hara K. et al.Characterization of two polymorphisms in the leukotriene C4 synthase gene in an Australian population of subjects with mild, moderate, and severe asthma.J Allergy Clin Immunol. 2004; 113: 889-895Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 7Kalayci O. Birben E. Sackesen C. Keskin O. Tahan F. Wechsler M.E. et al.ALOX5 promoter genotype, asthma severity and LTC production by eosinophils.Allergy. 2006; 61: 97-103Crossref PubMed Scopus (62) Google Scholar, 9Pillai S.G. Cousens D.J. Barnes A.A. Buckley P.T. Chiano M.N. Hosking L.K. et al.A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma.Pharmacogenetics. 2004; 14: 627-633Crossref PubMed Scopus (53) Google Scholar, 10Hong X. Zhou H. Tsai H.J. Wang X. Liu X. Wang B. et al.Cysteinyl leukotriene receptor 1 gene variation and risk of asthma.Eur Respir J. 2009; 33: 42-48Crossref PubMed Scopus (21) Google Scholar, 19Lima J.J. Zhang S. Grant A. Shao L. Tantisira K.G. Allayee H. et al.Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.Am J Respir Crit Care Med. 2006; 173: 379-385Crossref PubMed Scopus (215) Google Scholar, 20Telleria J.J. Blanco-Quiros A. Varillas D. Armentia A. Fernandez-Carvajal I. Jesus Alonso M. et al.ALOX5 promoter genotype and response to montelukast in moderate persistent asthma.Respir Med. 2008; 102: 857-861Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 21Drazen J.M. Yandava C.N. Dube L. Szczerback N. Hippensteel R. Pillari A. et al.Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.Nat Genet. 1999; 22: 168-170Crossref PubMed Scopus (520) Google Scholar, 23Tantisira K.G. Lima J. Sylvia J. Klanderman B. Weiss S.T. 5-Lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci.Pharmacogenet Genomics. 2009; 19: 244-247Crossref PubMed Scopus (65) Google Scholar, 24Kawagishi Y. Mita H. Taniguchi M. Maruyama M. Oosaki R. Higashi N. et al.Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma.J Allergy Clin Immunol. 2002; 109: 936-942Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar This strongly supports a heritable basis involving the leukotriene pathway for these asthma-related phenotypes. Although most of the studies have focused on the historical relationship with asthma, many of the association findings from the asthma literature are now being tested in the context of other diseases for which inflammation caused by enhanced leukotriene production has been implicated. This has broad implications for future studies focused on understanding the mechanistic basis of genetic variation within the leukotriene pathway. In addition, although most studies to date have focused on a relatively small group of pathway-specific genes, future studies in this area will likely include a broader range of genes with modulated through leukotrienes. These genes might be identified by using studies with microarray, integrative genomic, comparative genomic, and genome-wide association approaches. With the addition of reported relationships that require initial replication, it is clear that genetic and pharmacogenetic investigations involving the leukotriene pathway are in their formative stages.Table ILeukotriene pathway loci implicated in multiple asthma or asthma pharmacogenetic studiesGeneVariantAssociationsReferenceALOX5SP1-binding motifAsthma severityKalayci et al7Kalayci O. Birben E. Sackesen C. Keskin O. Tahan F. Wechsler M.E. et al.ALOX5 promoter genotype, asthma severity and LTC production by eosinophils.Allergy. 2006; 61: 97-103Crossref PubMed Scopus (62) Google ScholarSP1-binding motifResponse to 5-LO inhibitionDrazen et al21Drazen J.M. Yandava C.N. Dube L. Szczerback N. Hippensteel R. Pillari A. et al.Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.Nat Genet. 1999; 22: 168-170Crossref PubMed Scopus (520) Google ScholarSP1-binding motifResponse to leukotriene receptor antagonistsLima et al19Lima J.J. Zhang S. Grant A. Shao L. Tantisira K.G. Allayee H. et al.Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.Am J Respir Crit Care Med. 2006; 173: 379-385Crossref PubMed Scopus (215) Google ScholarSP1-binding motifResponse to leukotriene receptor antagonistsTelleria et al20Telleria J.J. Blanco-Quiros A. Varillas D. Armentia A. Fernandez-Carvajal I. Jesus Alonso M. et al.ALOX5 promoter genotype and response to montelukast in moderate persistent asthma.Respir Med. 2008; 102: 857-861Abstract Full Text Full Text PDF PubMed Scopus (67) Google ScholarALOX5rs2115819Response to leukotriene receptor antagonistsLima et al19Lima J.J. Zhang S. Grant A. Shao L. Tantisira K.G. Allayee H. et al.Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.Am J Respir Crit Care Med. 2006; 173: 379-385Crossref PubMed Scopus (215) Google Scholarrs2115819Response to 5-LO inhibitionTantisira et al23Tantisira K.G. Lima J. Sylvia J. Klanderman B. Weiss S.T. 5-Lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci.Pharmacogenet Genomics. 2009; 19: 244-247Crossref PubMed Scopus (65) Google ScholarCYSLTR2Met201ValAsthma affection in 2 populationsPillai et al9Pillai S.G. Cousens D.J. Barnes A.A. Buckley P.T. Chiano M.N. Hosking L.K. et al.A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma.Pharmacogenetics. 2004; 14: 627-633Crossref PubMed Scopus (53) Google ScholarCYSLTR1rs320995Asthma affection in 2 populations with meta-analysis in 5 studiesHong et al10Hong X. Zhou H. Tsai H.J. Wang X. Liu X. Wang B. et al.Cysteinyl leukotriene receptor 1 gene variation and risk of asthma.Eur Respir J. 2009; 33: 42-48Crossref PubMed Scopus (21) Google ScholarLTC4S−444 A/C promoterAsthma affectionKedda et al5Kedda M.A. Shi J. Duffy D. Phelps S. Yang I. O'Hara K. et al.Characterization of two polymorphisms in the leukotriene C4 synthase gene in an Australian population of subjects with mild, moderate, and severe asthma.J Allergy Clin Immunol. 2004; 113: 889-895Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar−444 A/C promoterAERDKawagishi et al24Kawagishi Y. Mita H. Taniguchi M. Maruyama M. Oosaki R. Higashi N. et al.Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma.J Allergy Clin Immunol. 2002; 109: 936-942Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar Open table in a new tab" @default.
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• W2016457422 title "Genetics and pharmacogenetics of the leukotriene pathway" @default.
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