Modest genetic influence on bronchodilator response: A study in healthy twins

D.L. Tarnoki; E. Medda; A.D. Tarnoki; A. Bikov; Z. Lazar; C. Fagnani; M.A. Stazi; K. Karlinger; Z. Garami; V. Berczi; I. Horvath

doi:10.3325/cmj.2015.56.152

Modest genetic influence on bronchodilator response: A study in healthy twins

D.L. Tarnoki, E. Medda, A.D. Tarnoki, A. Bikov, Z. Lazar, C. Fagnani, M.A. Stazi, K. Karlinger, Z. Garami, V. Berczi, I. Horvath

Division of Immunology, Immunity to Infection and Respiratory Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Aim: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. Methods: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 μg salbutamol). Univariate quantitative genetic modeling was performed. Results: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P <0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1- adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). Conclusion: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Original language	English
Pages (from-to)	152-158
Number of pages	7
Journal	Croatian Medical Journal
Volume	56
Issue number	2
DOIs	https://doi.org/10.3325/cmj.2015.56.152
Publication status	Published - 2015

Keywords

salbutamol
bronchodilating agent
adult
age
Article
body mass
dizygotic twins
drug response
environmental factor
female
forced expiratory volume
genetic association
heredity
human
human experiment
lung function
male
metered dose inhaler
monozygotic twins
phenotype
smoking habit
genetics
genotype environment interaction
middle aged
twins
Adult
Albuterol
Body Mass Index
Bronchodilator Agents
Female
Forced Expiratory Volume
Gene-Environment Interaction
Humans
Male
Middle Aged
Twins, Dizygotic
Twins, Monozygotic

Access to Document

10.3325/cmj.2015.56.152

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84928610953&doi=10.3325%2fcmj.2015.56.152&partnerID=40&md5=4217b949e1d9facd2d9e8190d480fe1c

Cite this

@article{91cffffff54e4a1f99ed0610c0b38dd7,

title = "Modest genetic influence on bronchodilator response: A study in healthy twins",

abstract = "Aim: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. Methods: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 μg salbutamol). Univariate quantitative genetic modeling was performed. Results: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P <0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1- adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). Conclusion: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.",

keywords = "salbutamol, bronchodilating agent, adult, age, Article, body mass, dizygotic twins, drug response, environmental factor, female, forced expiratory volume, genetic association, heredity, human, human experiment, lung function, male, metered dose inhaler, monozygotic twins, phenotype, smoking habit, genetics, genotype environment interaction, middle aged, twins, Adult, Albuterol, Body Mass Index, Bronchodilator Agents, Female, Forced Expiratory Volume, Gene-Environment Interaction, Humans, Male, Middle Aged, Twins, Dizygotic, Twins, Monozygotic",

author = "D.L. Tarnoki and E. Medda and A.D. Tarnoki and A. Bikov and Z. Lazar and C. Fagnani and M.A. Stazi and K. Karlinger and Z. Garami and V. Berczi and I. Horvath",

note = "Export Date: 31 October 2018 CODEN: CMEJE Correspondence Address: Tarnoki, D.L.; Department of Radiology and Oncotherapy, Semmelweis University, 78/A Ulloi street, Hungary Chemicals/CAS: salbutamol, 18559-94-9, 35763-26-9; Albuterol; Bronchodilator Agents References: Lorber, D.B., Kaltenborn, W., Burrows, B., Responses to isoproterenol in a general population sample (1978) Am Rev Respir Dis, 118, pp. 855-861. , Medline:736356; Watanabe, S., Renzetti Jr, A.D., Begin, R., Bigler, A.H., Airway responsiveness to a bronchodilator aerosol. I. Normal human subjects (1974) Am Rev Respir Dis, 109, pp. 530-537. , Medline:4823409; Brusasco, V., Crapo, R., Viegi, G., European Respiratory Society. Coming together: the ATS/ERS consensus on clinical pulmonary function testing (2005) Eur Respir J, 26, pp. 1-2. , Medline:15994380; Montes de Oca, M., Perez-Padilla, R., T{\'a}lamo, C., Halbert, R.J., Moreno, D., Lopez, M.V., Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: the PLATINO study (2010) Pulm Pharmacol Ther, 23, pp. 29-35. , Medline:19818867; Niggemann, B., Illi, S., Madloch, C., V{\"o}lkel, K., Lau, S., Bergmann, R., Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study (2001) Eur Respir J, 17, pp. 246-253. , Medline:11334127; Lima, J.J., Thomason, D.B., Mohamed, M.H., Eberle, L.V., Self, T.H., Johnson, J.A., Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics (1999) Clin Pharmacol Ther, 65, pp. 519-525. , Medline:10340917; Taylor, D.R., Epton, M.J., Kennedy, M.A., Smith, A.D., Iles, S., Miller, A.L., Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma (2005) Am J Respir Crit Care Med, 172, pp. 700-703. , Medline:15976384; Joos, L., Weir, T.D., Connett, J.E., Anthonisen, N.R., Woods, R., Par{\'e}, P.D., Polymorphisms in the beta2 adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers (2003) Thorax, 58, pp. 703-707. , Medline:12885990; Martinez, F.D., Graves, P.E., Baldini, M., Solomon, S., Erickson, R., Association between genetic polymorphisms of the beta2- adrenoceptor and response to albuterol in children with and without a history of wheezing (1997) J Clin Invest, 100, pp. 3184-3188. , Medline:9399966; Choudhry, S., Ung, N., Avila, P.C., Ziv, E., Nazario, S., Casal, J., Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma (2005) Am J Respir Crit Care Med, 171, pp. 563-570. , Medline:15557128; Niu, T., Rogus, J.J., Chen, C., Wang, B., Yang, J., Fang, Z., Familial aggregation of bronchodilator response: a communitybased study (2000) Am J Respir Crit Care Med, 162, pp. 1833-1837. , Medline:11069822; Susser, M., Susser, E., Indicators and designs in genetic epidemiology:separating heredity and environment (1987) Rev Epidemiol Sante Publique, 35, pp. 54-77. , Medline:3296037; Clarke, J.R., Jenkins, M.A., Hopper, J.L., Carlin, J.B., Mayne, C., Clayton, D.G., Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins (2000) Am J Respir Crit Care Med, 162, pp. 2188-2193. , Medline:11112136; Dav{\'e}, N.K., Hopp, R.J., Biven, R.E., Degan, J., Bewtra, A.K., Townley, R.G., Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents (1990) J Allergy Clin Immunol, 86, pp. 147-153. , Medline:2200819; Hopp, R.J., Bewtra, A.K., Watt, G.D., Nair, N.M., Townley, R.G., Genetic analysis of allergic disease in twins (1984) J Allergy Clin Immunol, 73, pp. 265-270. , Medline:6538209; Lund, M.B., Kongerud, J., Nystad, W., Boe, J., Harris, J.R., Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins (2007) Eur Respir J, 29, pp. 292-298. , Medline:17079261; Svartengren, M., Ericsson, C.H., Philipson, K., Mossberg, B., Camner, P., Tracheobronchial clearance in asthma-discordant monozygotic twins (1989) Respiration, 56, pp. 70-79. , Medline:2690236; Zamel, N., Leroux, M., Vanderdoelen, J.L., Airway response to inhaled methacholine in healthy nonsmoking twins (1984) J Appl Physiol, 56, pp. 936-939. , Medline:6373690; Anthonisen, N.R., Lindgren, P.G., Tashkin, D.P., Kanner, R.E., Scanlon, P.D., Connett, J.E., Bronchodilator response in the lung health study over 11 yrs (2005) Eur Respir J, 26, pp. 45-51. , Medline:15994388; Littvay, L., M{\'e}tneki, J., Tarnoki, A.D., Tarnoki, D.L., The Hungarian Twin Registry (2013) Twin Res Hum Genet, 16, pp. 185-189. , Medline:23084033; Kyvik, K.O., Green, A., Beck-Nielsen, H., The new Danish twin register:establishment and analysis of twinning rates (1995) Int J Epidemiol, 24, pp. 589-596. , Medline:7672901; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338. , Medline:16055882; Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R.O., Burgos, F., Casaburi, R., Interpretative strategies for lung function tests (2005) Eur Respir J, 26, pp. 948-968. , Medline:16264058; Neale, M.C., Michael, C., Cardon, L.R., (1992) Methodology for genetic studies of twins and families, , Dordrecht, Netherlands: Kluwer; Spector, T.D., Snieder, H., MacGregor, A.J., (2000) Advances in twin and sibpair analysis, , London: Greenwich Medical Media; McArdle, J.J., Hamagami, F., Structural equation models for evaluating dynamic concepts within longitudinal twin analyses (2003) Behav Genet, 33, pp. 137-159. , Medline:14574148; Neale, M.C., Boker, S.M., Xie, G., Maes, H., (2003) Mx: statistical modeling, , 6th edition). Richmond, VA, USA: Department of Psychiatry, Virginia Commonwealth University; Dales, R.E., Spitzer, W.O., Tousignant, P., Schechter, M., Suissa, S., Clinical interpretation of airway response to a bronchodilator. Epidemiologic considerations (1988) Am Rev Respir Dis, 138, pp. 317-320. , Medline:3195831; Duffy, D.L., Martin, N.G., Battistutta, D., Hopper, J.L., Mat-hews, J.D., Genetics of asthma and hay fever in Australian twins (1990) Am Rev Respir Dis, 142, pp. 1351-1358. , Medline:2252253; Harris, J.R., Magnus, P., Samuelsen, S.O., Tambs, K., No evidence for effects of family environment on asthma.A retrospective study of Norwegian twins (1997) Am J Respir Crit Care Med, 156, pp. 43-49. , Medline:9230724; Laitinen, T., Rasanen, M., Kaprio, J., Koskenvuo, M., Laitinen, L.A., Importance of genetic factors in adolescent asthma (1998) Am J Respir Crit Care Med, 157, pp. 1073-1078. , Medline:9563721; Huovinen, E., Kaprio, J., Laitinen, L.A., Koskenvuo, M., Social predictors of adult asthma: a co-twin case-control study (2001) Thorax, 56, pp. 234-236. , Medline:11182018; Nystad, W., Roysamb, E., Magnus, P., Tambs, K., Harris, J.R., A comparison of genetic and environmental variance structures for asthma, hay fever and eczema with symptoms of the same diseases:a study of Norwegian twins (2005) Int J Epidemiol, 34, pp. 1302-1309. , Medline:15831566; Fagnani, C., Annesi-Maesano, I., Brescianini, S., D'Ippolito, C., Medda, E., Nistic{\v n}, L., Heritability and shared genetic effects of asthma and hay fever: an Italian study of young twins (2008) Twin Res Hum Genet, 11, pp. 121-131. , Medline:18361712; Nikolajev, K., Korppi, M., Remes, K., L{\"a}nsimies, E., Jokela, V., Heinonen, K., Determinants of bronchial responsiveness to methacholine at school age in twin pairs (2002) Pediatr Pulmonol, 33, pp. 167-173. , Medline:11836795; Duffy, D., The genetic epidemiology of asthma (1997) Epidemiol Rev, 19, pp. 129-143. , Medline:9360910; Koh, Y.Y., Kang, E.K., Kang, H., Yoo, Y., Park, Y., Kim, C.K., Bronchial hyperresponsiveness in adolescents with long-term asthma remission: importance of a Family history of bronchial hyperresponsiveness (2003) Chest, 124, pp. 819-825. , Medline:12970003; Palmer, L.J., Burton, P.R., Faux, J.A., James, A.L., Musk, A.W., Cookson, W.O., Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness (2000) Am J Respir Crit Care Med, 161, pp. 1836-1843. , Medline:10852754; Postma, D.S., Koppelman, G.H., Meyers, D.A., The genetics of atopy and airway hyperresponsiveness (2000) Am J Respir Crit Care Med, 162, pp. 118-123. , Medline:10988165; Raby, B.A., Van Steen, K., Lasky-Su, J., Tantisira, K., Kaplan, F., Weiss, S.T., Importin-13 genetic variation is associated with improved airway responsiveness in childhood asthma (2009) Respir Res, 10, p. 67. , Medline:19619331; Schwartz, J., Schindler, C., Zemp, E., Perruchoud, A.P., Zellweger, J.P., W{\"u}thrich, B., Predictors of methacholine responsiveness in a general population (2002) Chest, 122, pp. 812-820. , Medline:12226018; Posthuma, D., Boomsma, D.I., A note on the statistical power in extended twin designs (2000) Behav Genet, 30, pp. 147-158. , Medline:10979605",

year = "2015",

doi = "10.3325/cmj.2015.56.152",

language = "English",

volume = "56",

pages = "152--158",

journal = "Croatian Medical Journal",

issn = "0353-9504",

publisher = "Medicinska Naklada d.o.o",

number = "2",

}

TY - JOUR

T1 - Modest genetic influence on bronchodilator response

T2 - A study in healthy twins

AU - Tarnoki, D.L.

AU - Medda, E.

AU - Tarnoki, A.D.

AU - Bikov, A.

AU - Lazar, Z.

AU - Fagnani, C.

AU - Stazi, M.A.

AU - Karlinger, K.

AU - Garami, Z.

AU - Berczi, V.

AU - Horvath, I.

N1 - Export Date: 31 October 2018 CODEN: CMEJE Correspondence Address: Tarnoki, D.L.; Department of Radiology and Oncotherapy, Semmelweis University, 78/A Ulloi street, Hungary Chemicals/CAS: salbutamol, 18559-94-9, 35763-26-9; Albuterol; Bronchodilator Agents References: Lorber, D.B., Kaltenborn, W., Burrows, B., Responses to isoproterenol in a general population sample (1978) Am Rev Respir Dis, 118, pp. 855-861. , Medline:736356; Watanabe, S., Renzetti Jr, A.D., Begin, R., Bigler, A.H., Airway responsiveness to a bronchodilator aerosol. I. Normal human subjects (1974) Am Rev Respir Dis, 109, pp. 530-537. , Medline:4823409; Brusasco, V., Crapo, R., Viegi, G., European Respiratory Society. Coming together: the ATS/ERS consensus on clinical pulmonary function testing (2005) Eur Respir J, 26, pp. 1-2. , Medline:15994380; Montes de Oca, M., Perez-Padilla, R., Tálamo, C., Halbert, R.J., Moreno, D., Lopez, M.V., Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: the PLATINO study (2010) Pulm Pharmacol Ther, 23, pp. 29-35. , Medline:19818867; Niggemann, B., Illi, S., Madloch, C., Völkel, K., Lau, S., Bergmann, R., Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study (2001) Eur Respir J, 17, pp. 246-253. , Medline:11334127; Lima, J.J., Thomason, D.B., Mohamed, M.H., Eberle, L.V., Self, T.H., Johnson, J.A., Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics (1999) Clin Pharmacol Ther, 65, pp. 519-525. , Medline:10340917; Taylor, D.R., Epton, M.J., Kennedy, M.A., Smith, A.D., Iles, S., Miller, A.L., Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma (2005) Am J Respir Crit Care Med, 172, pp. 700-703. , Medline:15976384; Joos, L., Weir, T.D., Connett, J.E., Anthonisen, N.R., Woods, R., Paré, P.D., Polymorphisms in the beta2 adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers (2003) Thorax, 58, pp. 703-707. , Medline:12885990; Martinez, F.D., Graves, P.E., Baldini, M., Solomon, S., Erickson, R., Association between genetic polymorphisms of the beta2- adrenoceptor and response to albuterol in children with and without a history of wheezing (1997) J Clin Invest, 100, pp. 3184-3188. , Medline:9399966; Choudhry, S., Ung, N., Avila, P.C., Ziv, E., Nazario, S., Casal, J., Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma (2005) Am J Respir Crit Care Med, 171, pp. 563-570. , Medline:15557128; Niu, T., Rogus, J.J., Chen, C., Wang, B., Yang, J., Fang, Z., Familial aggregation of bronchodilator response: a communitybased study (2000) Am J Respir Crit Care Med, 162, pp. 1833-1837. , Medline:11069822; Susser, M., Susser, E., Indicators and designs in genetic epidemiology:separating heredity and environment (1987) Rev Epidemiol Sante Publique, 35, pp. 54-77. , Medline:3296037; Clarke, J.R., Jenkins, M.A., Hopper, J.L., Carlin, J.B., Mayne, C., Clayton, D.G., Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins (2000) Am J Respir Crit Care Med, 162, pp. 2188-2193. , Medline:11112136; Davé, N.K., Hopp, R.J., Biven, R.E., Degan, J., Bewtra, A.K., Townley, R.G., Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents (1990) J Allergy Clin Immunol, 86, pp. 147-153. , Medline:2200819; Hopp, R.J., Bewtra, A.K., Watt, G.D., Nair, N.M., Townley, R.G., Genetic analysis of allergic disease in twins (1984) J Allergy Clin Immunol, 73, pp. 265-270. , Medline:6538209; Lund, M.B., Kongerud, J., Nystad, W., Boe, J., Harris, J.R., Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins (2007) Eur Respir J, 29, pp. 292-298. , Medline:17079261; Svartengren, M., Ericsson, C.H., Philipson, K., Mossberg, B., Camner, P., Tracheobronchial clearance in asthma-discordant monozygotic twins (1989) Respiration, 56, pp. 70-79. , Medline:2690236; Zamel, N., Leroux, M., Vanderdoelen, J.L., Airway response to inhaled methacholine in healthy nonsmoking twins (1984) J Appl Physiol, 56, pp. 936-939. , Medline:6373690; Anthonisen, N.R., Lindgren, P.G., Tashkin, D.P., Kanner, R.E., Scanlon, P.D., Connett, J.E., Bronchodilator response in the lung health study over 11 yrs (2005) Eur Respir J, 26, pp. 45-51. , Medline:15994388; Littvay, L., Métneki, J., Tarnoki, A.D., Tarnoki, D.L., The Hungarian Twin Registry (2013) Twin Res Hum Genet, 16, pp. 185-189. , Medline:23084033; Kyvik, K.O., Green, A., Beck-Nielsen, H., The new Danish twin register:establishment and analysis of twinning rates (1995) Int J Epidemiol, 24, pp. 589-596. , Medline:7672901; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338. , Medline:16055882; Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R.O., Burgos, F., Casaburi, R., Interpretative strategies for lung function tests (2005) Eur Respir J, 26, pp. 948-968. , Medline:16264058; Neale, M.C., Michael, C., Cardon, L.R., (1992) Methodology for genetic studies of twins and families, , Dordrecht, Netherlands: Kluwer; Spector, T.D., Snieder, H., MacGregor, A.J., (2000) Advances in twin and sibpair analysis, , London: Greenwich Medical Media; McArdle, J.J., Hamagami, F., Structural equation models for evaluating dynamic concepts within longitudinal twin analyses (2003) Behav Genet, 33, pp. 137-159. , Medline:14574148; Neale, M.C., Boker, S.M., Xie, G., Maes, H., (2003) Mx: statistical modeling, , 6th edition). Richmond, VA, USA: Department of Psychiatry, Virginia Commonwealth University; Dales, R.E., Spitzer, W.O., Tousignant, P., Schechter, M., Suissa, S., Clinical interpretation of airway response to a bronchodilator. Epidemiologic considerations (1988) Am Rev Respir Dis, 138, pp. 317-320. , Medline:3195831; Duffy, D.L., Martin, N.G., Battistutta, D., Hopper, J.L., Mat-hews, J.D., Genetics of asthma and hay fever in Australian twins (1990) Am Rev Respir Dis, 142, pp. 1351-1358. , Medline:2252253; Harris, J.R., Magnus, P., Samuelsen, S.O., Tambs, K., No evidence for effects of family environment on asthma.A retrospective study of Norwegian twins (1997) Am J Respir Crit Care Med, 156, pp. 43-49. , Medline:9230724; Laitinen, T., Rasanen, M., Kaprio, J., Koskenvuo, M., Laitinen, L.A., Importance of genetic factors in adolescent asthma (1998) Am J Respir Crit Care Med, 157, pp. 1073-1078. , Medline:9563721; Huovinen, E., Kaprio, J., Laitinen, L.A., Koskenvuo, M., Social predictors of adult asthma: a co-twin case-control study (2001) Thorax, 56, pp. 234-236. , Medline:11182018; Nystad, W., Roysamb, E., Magnus, P., Tambs, K., Harris, J.R., A comparison of genetic and environmental variance structures for asthma, hay fever and eczema with symptoms of the same diseases:a study of Norwegian twins (2005) Int J Epidemiol, 34, pp. 1302-1309. , Medline:15831566; Fagnani, C., Annesi-Maesano, I., Brescianini, S., D'Ippolito, C., Medda, E., Nisticň, L., Heritability and shared genetic effects of asthma and hay fever: an Italian study of young twins (2008) Twin Res Hum Genet, 11, pp. 121-131. , Medline:18361712; Nikolajev, K., Korppi, M., Remes, K., Länsimies, E., Jokela, V., Heinonen, K., Determinants of bronchial responsiveness to methacholine at school age in twin pairs (2002) Pediatr Pulmonol, 33, pp. 167-173. , Medline:11836795; Duffy, D., The genetic epidemiology of asthma (1997) Epidemiol Rev, 19, pp. 129-143. , Medline:9360910; Koh, Y.Y., Kang, E.K., Kang, H., Yoo, Y., Park, Y., Kim, C.K., Bronchial hyperresponsiveness in adolescents with long-term asthma remission: importance of a Family history of bronchial hyperresponsiveness (2003) Chest, 124, pp. 819-825. , Medline:12970003; Palmer, L.J., Burton, P.R., Faux, J.A., James, A.L., Musk, A.W., Cookson, W.O., Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness (2000) Am J Respir Crit Care Med, 161, pp. 1836-1843. , Medline:10852754; Postma, D.S., Koppelman, G.H., Meyers, D.A., The genetics of atopy and airway hyperresponsiveness (2000) Am J Respir Crit Care Med, 162, pp. 118-123. , Medline:10988165; Raby, B.A., Van Steen, K., Lasky-Su, J., Tantisira, K., Kaplan, F., Weiss, S.T., Importin-13 genetic variation is associated with improved airway responsiveness in childhood asthma (2009) Respir Res, 10, p. 67. , Medline:19619331; Schwartz, J., Schindler, C., Zemp, E., Perruchoud, A.P., Zellweger, J.P., Wüthrich, B., Predictors of methacholine responsiveness in a general population (2002) Chest, 122, pp. 812-820. , Medline:12226018; Posthuma, D., Boomsma, D.I., A note on the statistical power in extended twin designs (2000) Behav Genet, 30, pp. 147-158. , Medline:10979605

PY - 2015

Y1 - 2015

N2 - Aim: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. Methods: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 μg salbutamol). Univariate quantitative genetic modeling was performed. Results: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P <0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1- adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). Conclusion: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

AB - Aim: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. Methods: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 μg salbutamol). Univariate quantitative genetic modeling was performed. Results: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P <0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1- adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). Conclusion: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

KW - salbutamol

KW - bronchodilating agent

KW - adult

KW - age

KW - Article

KW - body mass

KW - dizygotic twins

KW - drug response

KW - environmental factor

KW - female

KW - forced expiratory volume

KW - genetic association

KW - heredity

KW - human

KW - human experiment

KW - lung function

KW - male

KW - metered dose inhaler

KW - monozygotic twins

KW - phenotype

KW - smoking habit

KW - genetics

KW - genotype environment interaction

KW - middle aged

KW - twins

KW - Adult

KW - Albuterol

KW - Body Mass Index

KW - Bronchodilator Agents

KW - Female

KW - Forced Expiratory Volume

KW - Gene-Environment Interaction

KW - Humans

KW - Male

KW - Middle Aged

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.3325/cmj.2015.56.152

DO - 10.3325/cmj.2015.56.152

M3 - Article

SN - 0353-9504

VL - 56

SP - 152

EP - 158

JO - Croatian Medical Journal

JF - Croatian Medical Journal

IS - 2

ER -

Modest genetic influence on bronchodilator response: A study in healthy twins

Abstract

Keywords

Access to Document

Fingerprint

Cite this