Abstract
Lung disease and Pseudomonas aeruginosa (P. aeruginosa) airway colonization represent a major cause of morbidity and mortality in cystic fibrosis (CF). Human β-defensin (hBD)-1 is believed to play an important role in mucosal innate immunity in the lung. This study aimed to investigate whether three single-nucleotide polymorphisms (SNPs) in the 5′-untranslated region of DEFB1, G-52A, C-44G and G-20A were associated with P. aeruginosa airway colonization in CF. A total of 224 CF patients and 196 control subjects were studied. DEFB1 SNPs were characterized by restriction fragment length polymorphisms. Patients' sputum samples were collected and analyzed by standard methods. Single SNP analysis suggested that CF patients carrying the −52AA and the −20GG genotypes had a higher rate of P. aeruginosa airway colonization than patients homozygous and heterozygous for the −52G and −20A alleles (P=0.01 and P=0.007, respectively). A significant association between the ACG haplotype and chronic P. aeruginosa infection was also identified (odds ratio (95% confidence interval): 3.00 (1.42–6.36), P=0.004). These results indicate that variant alleles in DEFB1 might contribute to the colonization of P. aeruginosa in CF.
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References
Davis PB, Drumm M, Konstan MW . Cystic fibrosis. Am J Respir Crit Care Med 1996; 154: 1229–1256.
Ratjen F, Döring G . Cystic fibrosis. Lancet 2003; 361: 681–689.
Burns JL, Gibson RL, McNamara S, Yim D, Emerson J, Rosenfeld M et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis 2001; 183: 444–452.
Liu L, Zhao C, Heng HH, Ganz T . The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics 1997; 43: 316–320.
Ganz T . Defensins and host defense. Science 1999; 286: 420–421.
Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525–528.
Travis SM, Singh PK, Welsh MJ . Antimicrobial peptides and proteins in the innate defense of the airway surface. Curr Opin Immunol 2001; 13: 89–95.
Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM . Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 1997; 88: 553–560.
Smith JJ, Travis SM, Greenberg EP, Welsh MJ . Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996; 85: 229–236.
Bals R, Weiner DJ, Meegalla RL, Accurso F, Wilson JM . Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid. Am J Respir Cell Mol Biol 2001; 25: 21–25.
Accurso FJ, Sontag MK . Seeking modifier genes in cystic fibrosis. Am J Respir Crit Care Med 2003; 167: 289–290.
Davies JC, Griesenbach U, Alton E . Modifier genes in cystic fibrosis. Pediatr Pulmonol 2005; 39: 383–391.
Salvatore F, Scudiero O, Castaldo G . Genotype–phenotype correlation in cystic fibrosis: the role of modifier genes. Am J Med Genet 2002; 111: 88–95.
Vankeerberghen A, Scudiero O, De Boeck K, Macek Jr M, Pignatti PF, Van Hul N et al. Distribution of human-defensin polymorphisms in various control and cystic fibrosis populations. Genomics 2005; 85: 574–581.
Innate Immunity in Heart, Lung, Blood Disease: Programs for Genomic Applications. IIPGA Genetic Data on DEFB1. Available at: http://innateimmunity.net/IIPGA2/PGAs/InnateImmunity/DEFB1/ and publicly accessed on 27 October 2005.
Dork T, Stuhrmann M . Polymorphisms of the human beta-defensin-1 gene. Mol Cell Probes 1998; 12: 171–173.
Leung TF, Li CY, Liu EK, Tang NL, Chan IM, Yung E et al. Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children. Genes Immun 2006; 7: 59–64.
Urquhart DS, Allen J, Elrayess M, Fidler K, Klein N, Jaffé A . Modifier effect of Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis. Arch Immunol Ther Exp 2006; 54: 271–276.
Garred P, Pressler T, Madsen HO, Frederiksen B, Svejgaard A, Hoiby N et al. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest 1999; 104: 431–437.
Braida L, Boniotto M, Pontillo A, Tovo PA, Amoroso A, Crovella S . A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children. AIDS 2004; 18: 1598–1600.
Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA . Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 2003; 41: 90–96.
Wallace AM, He JQ, Burkett KM, Ruan J, Connett JE, Anthonisen NR et al. Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study. Respir Res 2006; 7: 76–83.
Gibson LE, Cooke RE . A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 1959; 23: 545–549.
Kulczycki LL, Kostuch M, Bellanti JA . A clinical prospective of cystic fibrosis and new genetic findings: relationship of CFTR mutations to genotype–phenotype manifestations. Am J Med Genet 2003; 116: 262–267.
Frederiksen B, Koch C, Hoiby N . Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol 1999; 28: 159–166.
Stephens M, Smith NJ, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978–989.
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.
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This study was supported by grant for research from the University of Bari.
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Tesse, R., Cardinale, F., Santostasi, T. et al. Association of β-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis. Genes Immun 9, 57–60 (2008). https://doi.org/10.1038/sj.gene.6364440
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DOI: https://doi.org/10.1038/sj.gene.6364440
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