title: Polymorphisms in surfactant protein-D are associated with chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and abnormal inflammatory responses to noxious stimuli. Surfactant protein-D (SFTPD) is immunomodulatory and essential to host defense. We hypothesized that polymorphisms in SFTPD could influence the susceptibility to COPD. We genotyped six single-nucleotide polymorphisms (SNPs) in surfactant protein D in 389 patients with COPD in the National Emphysema Treatment Trial (NETT) and 472 smoking control subjects from the Normative Aging Study (NAS). Case-control association analysis was performed using Cochran-Armitage trend tests and multivariate logistic regression. The replication of significant associations was attempted in the Boston Early-Onset COPD Study, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and the Bergen Cohort. We also correlated SFTPD genotypes with serum concentrations of surfactant protein-D (SP-D) in the ECLIPSE Study. In the NETT-NAS case-control analysis, four SFTPD SNPs were associated with susceptibility to COPD: rs2245121 (P = 0.01), rs911887 (P = 0.006), rs6413520 (P = 0.004), and rs721917 (P = 0.006). In the family-based analysis of the Boston Early-Onset COPD Study, rs911887 was associated with prebronchodilator and postbronchodilator FEV(1) (P = 0.003 and P = 0.02, respectively). An intronic SNP in SFTPD, rs7078012, was associated with COPD in the ECLIPSE Study and the Bergen Cohort. Multiple SFTPD SNPs were associated with serum SP-D concentrations in the ECLIPSE Study. We demonstrated an association of polymorphisms in SFTPD with COPD in multiple populations. We demonstrated a correlation between SFTPD SNPs and SP-D protein concentrations. The SNPs associated with COPD and SP-D concentrations differed, suggesting distinct genetic influences on susceptibility to COPD and SP-D concentrations.
authors.affiliation: Pulmonary and Critical Care Medicine, Morehouse School of Medicine, Atlanta, GA 30310, USA. mforeman@msm.edu
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Foreman
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Kong
authors.forename: Dawn L
authors.initials: DL
authors.lastname: DeMeo
authors.forename: Sreekumar G
authors.initials: SG
authors.lastname: Pillai
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Amund
authors.initials: A
authors.lastname: Gulsvik
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shapiro
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D000368:Aged; D000375:Aging; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D
references.citation: Eur Respir J. 2010 Apr;35(4):768-75
references.pmid: 19797132
references.citation: PLoS Biol. 2008 Nov 11;6(11):e266
references.pmid: 19007302
references.citation: Chest. 2004 Nov;126(5):1443-51
references.pmid: 15539711
references.citation: Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55
references.pmid: 17507545
references.citation: Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1860-6
references.pmid: 8520747
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L1010-7
references.pmid: 16361352
references.citation: Clin Chem. 2001 Feb;47(2):164-72
references.pmid: 11159763
references.citation: Scand J Immunol. 2006 Dec;64(6):633-8
references.pmid: 17083619
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Hum Hered. 2002;53(3):146-52
references.pmid: 12145550
references.citation: FEBS Lett. 2005 Aug 15;579(20):4449-53
references.pmid: 16061223
references.citation: Respirology. 2006 Jan;11 Suppl:S37-40
references.pmid: 16423269
references.citation: J Immunol. 2001 Jun 15;166(12):7514-9
references.pmid: 11390505
references.citation: Immunology. 2002 Jul;106(3):389-94
references.pmid: 12100727
references.citation: Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1770-8
references.pmid: 9620904
references.citation: J Biol Chem. 2004 Jul 16;279(29):30871-9
references.pmid: 15123664
references.citation: Am J Respir Crit Care Med. 2007 Jul 15;176(2):167-73
references.pmid: 17446335
references.citation: PLoS Genet. 2009 Mar;5(3):e1000421
references.pmid: 19300482
references.citation: J Immunol. 2002 Oct 1;169(7):3978-86
references.pmid: 12244199
references.citation: Am J Respir Crit Care Med. 2008 Jun 1;177(11):1207-14
references.pmid: 18310480
references.citation: Clin Chim Acta. 1997 Oct 31;266(2):157-71
references.pmid: 9437544
references.citation: Mol Immunol. 2005 Feb;42(3):279-87
references.pmid: 15589315
references.citation: Proc Am Thorac Soc. 2005;2(5):403-11
references.pmid: 16322590
references.citation: COPD. 2007 Dec;4(4):347-53
references.pmid: 18027162
references.citation: J Immunol Methods. 1994 Aug 1;173(2):157-64
references.pmid: 8046250
references.citation: Am J Respir Crit Care Med. 2008 Jun 1;177(11):1177-8
references.pmid: 18487618
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: JAMA. 1997 Nov 5;278(17):1426-31
references.pmid: 9356001
references.citation: J Thorac Cardiovasc Surg. 1999 Sep;118(3):518-28
references.pmid: 10469970
references.citation: Nucleic Acids Res. 2004 May 18;32(9):e71
references.pmid: 15150323
references.citation: Am J Respir Cell Mol Biol. 2009 Sep;41(3):324-31
references.pmid: 19131638
references.citation: Respir Med. 2005 Dec;99(12):1583-90
references.pmid: 16291079
references.citation: Respir Res. 2008 Jan 28;9:13
references.pmid: 18226251
references.citation: N Engl J Med. 2001 Oct 11;345(15):1075-83
references.pmid: 11596586
references.citation: Eur Respir J. 2008 Apr;31(4):869-73
references.pmid: 18216052
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):5972-7
references.pmid: 10801980
references.citation: J Immunol. 2005 Apr 15;174(8):4953-9
references.pmid: 15814723
references.citation: Am Rev Respir Dis. 1981 Jun;123(6):659-64
references.pmid: 7271065
references.citation: Eur Respir J. 2001 Sep;18(3):482-90
references.pmid: 11589345
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Respir Res. 2006 Jun 01;7:85
references.pmid: 16740162
references.citation: Am J Hum Genet. 1998 Jul;63(1):259-66
references.pmid: 9634505
references.citation: Eur Respir J. 2009 Jul;34(1):95-102
references.pmid: 19164344
references.citation: Am J Respir Cell Mol Biol. 2005 Jul;33(1):71-8
references.pmid: 15817713
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Immunogenetics. 2005 Apr;57(1-2):1-7
references.pmid: 15700120
references.citation: Respir Res. 2007 Oct 03;8:70
references.pmid: 17915009
references.citation: BMC Pulm Med. 2007 Oct 08;7:13
references.pmid: 17922919
references.citation: Am J Respir Crit Care Med. 2006 Oct 15;174(8):886-93
references.pmid: 16888288
references.citation: Proc Am Thorac Soc. 2007 Jul;4(3):252-7
references.pmid: 17607008
references.citation: J Immunol. 2005 Feb 1;174(3):1532-8
references.pmid: 15661913
references.citation: Scand J Immunol. 2007 Jul;66(1):71-76
references.pmid: 17587348