Association Analysis of Brain-Derived Neurotrophic Factor Gene Polymorphisms in Asthmatic FamiliesSzczepankiewicz A.a · Rose-Zerilli M.J.b, c · Barton S.J.c · Holgate S.T.c · Holloway J.W.b, c
aDepartment of Pediatric Pulmonology, Allergy and Clinical Immunology, Third Department of Pediatrics, Poznan University of Medical Sciences, Poznan, Poland; bDivisions of Human Genetics and cInfection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, UK
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Background: A role for neuronal modulation of inflammation and airway hyper-responsiveness has been well described in asthma, and neurotrophins provide the link between inflammation and neuronal dysfunction. Brain-derived neurotrophic factor (BDNF) is an important mediator in this interaction. The aim of this study was to analyze the possible relationship between polymorphisms of the gene encoding BDNF and susceptibility to asthma. Methods: 341 families with at least 2 siblings with asthma were genotyped for 4 BDNF polymorphisms (rs6265, rs2030324, rs988748 and rs7124442). Results: Analysis by family-based association tests revealed no significant association between any polymorphisms analyzed and asthma susceptibility. Furthermore, BDNF polymorphism was not associated with asthma-related phenotypes such as FEV1 % predicted, bronchial hyper-responsiveness, IgE level, asthma and atopy severity scores. Conclusions: Our results suggest that genetic variation in the BDNF gene does not contribute significantly to asthma susceptibility or severity.
© 2009 S. Karger AG, Basel
- Braun A, Lommatzsch M, Mannsfeldt A, Neuhaus-Steinmetz U, Fischer A, Schnoy N, Lewin GR, Renz H: Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation. Am J Respir Cell Mol Biol 1999;21:537–546.
- Miller FD, Kaplan DR: Neurobiology: Trk makes the retrograde. Science 2002;295:1471–1473.
- Nassenstein C, Braun A, Erpenbeck VJ, Lommatzsch M, Schmidt S, Krug N, Luttmann W, Renz H, Virchow JC Jr: The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma. J Exp Med 2003;198:455–467.
- Noga O, Englmann C, Hanf G, Grutzkau A, Guhl S, Kunkel G: Activation of the specific neurotrophin receptors trka, trkb and trkc influences the function of eosinophils. Clin Exp Allergy 2002;32:1348–1354.
- Braun A, Appel E, Baruch R, Herz U, Botchkarev V, Paus R, Brodie C, Renz H: Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Immunol 1998;28:3240–3251.
- Undem BJ, Hunter DD, Liu M, Haak-Frendscho M, Oakragly A, Fischer A: Allergen-induced sensory neuroplasticity in airways. Int Arch Allergy Immunol 1999;118:150–153.
- de Vries A, Dessing MC, Engels F, Henricks PA, Nijkamp FP: Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med 1999;159:1541–1544.
- Kerzel S, Path G, Nockher WA, Quarcoo D, Raap U, Groneberg DA, Dinh QT, Fischer A, Braun A, Renz H: Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol 2003;28:170–178.
- Hoyle GW, Graham RM, Finkelstein JB, Nguyen KP, Gozal D, Friedman M: Hyperinnervation of the airways in transgenic mice overexpressing nerve growth factor. Am J Respir Cell Mol Biol 1998;18:149–157.
- Virchow JC, Julius P, Lommatzsch M, Luttmann W, Renz H, Braun A: Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation. Am J Respir Crit Care Med 1998;158:2002–2005.
- Noga O, Hanf G, Schaper C, O’Connor A, Kunkel G: The influence of inhalative corticosteroids on circulating nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in allergic asthmatics. Clin Exp Allergy 2001;31:1906–1912.
- Lommatzsch M, Schloetcke K, Klotz J, Schuhbaeck K, Zingler D, Zingler C, Schulte-Herbruggen O, Gill H, Schuff-Werner P, Virchow JC: Brain-derived neurotrophic factor in platelets and airflow limitation in asthma. Am J Respir Crit Care Med 2005;171:115–120.
- Noga O, Peiser M, Altenahr M, Knieling H, Wanner R, Hanf G, Grosse R, Suttorp N: Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor. Clin Exp Allergy 2007;37:1701–1708.
- Maisonpierre PC, Le Beau MM, Espinosa R 3rd, Ip NY, Belluscio L, de la Monte SM, Squinto S, Furth ME, Yancopoulos GD: Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. Genomics 1991;10:558–568.
- Postma DS, Meyers DA, Jongepier H, Howard TD, Koppelman GH, Bleecker ER: Genomewide screen for pulmonary function in 200 families ascertained for asthma. Am J Respir Crit Care Med 2005;172:446–452.
- Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M, Persson H: Multiple promoters direct tissue-specific expression of the rat bdnf gene. Neuron 1993;10:475–489.
- Okada T, Hashimoto R, Numakawa T, Iijima Y, Kosuga A, Tatsumi M, Kamijima K, Kato T, Kunugi H: A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene confers susceptibility to bipolar disorder and affects transcriptional activity. Mol Psychiatry 2006;11:695–703.
- Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 1999;22:231–238.
- Kunugi H, Ueki A, Otsuka M, Isse K, Hirasawa H, Kato N, Nabika T, Kobayashi S, Nanko S: A novel polymorphism of the brain- derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer’s disease. Mol Psychiatry 2001;6:83–86.
- Ribases M, Gratacos M, Armengol L, de Cid R, Badia A, Jimenez L, Solano R, Vallejo J, Fernandez F, Estivill X: Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Mol Psychiatry 2003;8:745– 751.
- Szczepankiewicz A, Breborowicz A, Skibinska M, Wilkosc M, Tomaszewska M, Hauser J: Association analysis of brain-derived neurotrophic factor gene polymorphisms in asthmatic children. Pediatr Allergy Immunol 2007;18:293–297.
- Sayers I, Barton S, Rorke S, Beghé B, Hayward B, Van Eerdewegh P, Keith T, Clough JB, Ye S, Holloway JW, Sampson AP, Holgate ST: Allelic association and functional studies of promoter polymorphism in the leukotriene c4 synthase gene (LTC4S) in asthma. Thorax 2003;58:417–424.
- Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP: Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002;418:426–430.
- Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR: The BDNF Val66Met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003;112:257–269.
- Horvath S, Xu X, Lake SL, Silverman EK, Weiss ST, Laird NM: Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics. Genet Epidemiol 2004;26:61–69.
- Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263–265.
- Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science 1996;273:1516–1517.
- Egan MF, Weinberger DR, Lu B: Schizophrenia. III. Brain-derived neurotrophic factor and genetic risk. Am J Psychiatry 2003;160:1242.
- Qian L, Zhao J, Shi Y, Zhao X, Feng G, Xu F, Zhu S, He L: Brain-derived neurotrophic factor and risk of schizophrenia: an association study and meta-analysis. Biochem Biophys Res Commun 2007;353:738–743.
- Schumacher J, Jamra RA, Becker T, Ohlraun S, Klopp N, Binder EB, Schulze TG, Deschner M, Schmal C, Hofels S, Zobel A, Illig T, Propping P, Holsboer F, Rietschel M, Nothen MM, Cichon S: Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 2005;58:307–314.
- Watanabe Y, Muratake T, Kaneko N, Nunokawa A, Someya T: No association between the brain-derived neurotrophic factor gene and schizophrenia in a Japanese population. Schizophr Res 2006;84:29–35.
- Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL: The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 2002;71:651–655.
- Sklar P, Gabriel SB, McInnis MG, Bennett P, Lim YM, Tsan G, Schaffner S, Kirov G, Jones I, Owen M, Craddock N, DePaulo JR, Lander ES: Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry 2002;7:579–593.
- Beuten J, Ma JZ, Payne TJ, Dupont RT, Quezada P, Huang W, Crews KM, Li MD: Significant association of BDNF haplotypes in European-American male smokers but not in European-American female or African-American smokers. Am J Med Genet B Neuropsychiatr Genet 2005;139B:73–80.
- Vepsalainen S, Castren E, Helisalmi S, Iivonen S, Mannermaa A, Lehtovirta M, Hanninen T, Soininen H, Hiltunen M: Genetic analysis of BDNF and TrkB gene polymorphisms in Alzheimer’s disease. J Neurol 2005;252:423–428.
- Joachim RA, Noga O, Sagach V, Hanf G, Fliege H, Kocalevent RD, Peters EM, Klapp BF: Correlation between immune and neuronal parameters and stress perception in allergic asthmatics. Clin Exp Allergy 2008;38:283–290.
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