Pharmacogenetic study of the effects of NK2R G231E G&gt;A and TBX21 H33Q C&gt;G polymorphisms on asthma control with inhaled corticosteroid treatment

Ym, Ye; Hy, Lee; Kim, Seung Hyun; Jee, Young Koo; Sk, Lee; Sh, Lee; Park, Hae‐Sim

doi:10.1111/j.1365-2710.2009.01054.x

Cited by 34 publications

(32 citation statements)

References 30 publications

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“…In addition, the pharmacogenetic effects of the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms on response to 3 months of ICS therapy have been previously investigated, and no significant genotypic effects were noted for FEV 1 or MMEF predicted values in the Korean population (17). Therefore, the pharmacogenetic effects of the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms on mono ICS therapy can be excluded.…”

Section: Resultsmentioning

confidence: 99%

Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy

Kim

Lee

et al. 2010

Journal of Clinical Pharmacy and Therapeutics

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Summary What is known and objective: Inhaled combination therapy composing of long‐acting β2‐agonist and corticosteroid has been widely applied in the management of asthma, but observed treatment responses vary. The aim of this study was to evaluate the pharmacogenetic effect of the adenylyl cyclase type 9 (ADCY9) gene polymorphism on combination therapy. Materials and methods: Eighty‐six mild to moderate Korean asthmatics were enrolled in this clinical trial. After the 2‐week ‘run‐in’ period, patients received budesonide (an inhaled corticosteroid) and formoterol (long‐acting β2‐agonist) during the following 12‐week active treatment period. Forced expiratory volume in 1 s (FEV1) and maximum mid‐expiratory flow (MMEF) levels were measured at all visits as primary outcome. ADCY9 (Ile772Met, 150127 C/T, 150130 C/T, 150397 C/T, 150479 C/T, TTTA 5/4) and β2‐adrenergic receptor (ADRB2, Arg16Gly) gene polymorphisms were genotyped. Results: Significant associations were observed between the ADCY9 single nucleotide polymorphisms and percent changes in FEV1 (Ile772Met T/C, P = 0·030) and MMEF (150397 C/T, P = 0·016) after 8 weeks of combination therapy. Haplotype associations were also observed with respect to percent changes in FEV1 after 8 weeks of therapy (Ht3[TTCC], P = 0·017). Additive therapeutic effect was observed in those with the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms in terms of percent change in FEV1 after 8 and 12 weeks of therapy (P = 0·002 and P = 0·027 respectively). What is new and conclusion: Our results suggest that ADCY9 gene polymorphisms may alone, and in combination with ADRB2 gene polymorphisms, contribute to individual response to combination therapy in mild to moderate asthmatics.

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Section: Resultsmentioning

confidence: 99%

Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy

Kim

Lee

et al. 2010

Journal of Clinical Pharmacy and Therapeutics

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“…Subsequently, Ye and colleagues demonstrated that the TBX21 (His33Gln) polymorphism was significantly associated with improved asthma control in the presence of corticosteroids, although the alternative allele to that described previously was associated with greater control in 53 Korean asthma patients during 5-12 weeks treatment [58]. In the same study, Ye and colleagues identified that Neurokinin 2 receptor (NK2R) SNP (rs77038916G/A, Gly231Glu) was associated with improved asthma control in the presence of corticosteroid, with the G allele (Gly) associated with greatest improvement [58] . Neurokinin A induces bronchoconstriction and inflammation, therefore modulation of the neurokinin receptor may influence the magnitude of these responses.…”

Section: Corticosteroidsmentioning

confidence: 92%

Genetic basis for personalized medicine in asthma

Portelli

Sayers²

2012

Expert Review of Respiratory Medicine

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“…Additional candidate genes found to be associated with altered beta agonist response in asthmatic children include ADCY9 150 and ARG1 159 with FEV1 change, and CRH2 148 and SPATS2L 149 with bronchodilator response. Additional candidate gene studies have also demonstrated altered asthma phenotypes in response to glucocorticoid therapies including CRH1 160 , STIP1 161 , TBX21 162,163 , ADCY9 150 164 , and ORDML3 165 .…”

Section: Clinical Implications and Personalized Medicinementioning

confidence: 99%

Genetics of Allergic Diseases

Ortiz¹,

Barnes²

2015

Immunology and Allergy Clinics of North America

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The allergic diseases are complex phenotypes for which a strong genetic basis has been firmly established. Genome-wide association studies (GWAS) has been widely employed in the field of allergic disease, and to date significant associations have been published for nearly 100 asthma genes/loci, in addition to multiple genes/loci for AD, AR and IgE levels, for which the overwhelming number of candidates are novel and have given a new appreciation for the role of innate as well as adaptive immune-response genes in allergic disease. A major outcome of GWAS in allergic disease has been the formation of national and international collaborations leading to consortia meta-analyses, and an appreciation for the specificity of genetic associations to sub-phenotypes of allergic disease. Molecular genetics has undergone a technological revolution, leading to next generation sequencing (NGS) strategies that are increasingly employed to hone in on the causal variants associated with allergic diseases. Unmet needs in the field include the inclusion of ethnically and racially diverse cohorts, and strategies for managing ‘big data’ that is an outcome of technological advances such as sequencing.

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Pharmacogenetic study of the effects of NK2R G231E G>A and TBX21 H33Q C>G polymorphisms on asthma control with inhaled corticosteroid treatment

Abstract: Our results suggest that NK2R G231E G>A and TBX21 H33Q C>G are genetic predictors of response to ICS, at least with respect to asthma control status and changes in FEV(1)%, in Korean patients with asthma. Further prospective validation of those associations is necessary.

Cited by 34 publications

References 30 publications

Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy

Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy

Genetic basis for personalized medicine in asthma

Genetics of Allergic Diseases

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