title: Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association.
  
  
  METHODS
  We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels.
  
  
  RESULTS
  None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively).
  
  
  CONCLUSIONS
  No single marker was significantly associated with either rate of lung function decline or serum CRP levels.
authors.affiliation: Department of Respiratory and Critical Medicine, West China Hospital of Sichuan University Chengdu, Sichuan Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Karey
authors.initials: K
authors.lastname: Shumansky
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Loubna
authors.initials: L
authors.lastname: Akhabir
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota Minneapolis, MN, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.affiliation: Faculty of Medicine, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.affiliation: Department of Respiratory and Critical Medicine, West China Hospital of Sichuan University Chengdu, Sichuan Province, China ; Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics*; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects*
chemical_list: D007375:Interleukin-1; D002097:C-Reactive Protein
keywords: C-reactive protein; Chronic obstructive pulmonary disease (COPD); IL1 gene cluster; forced expiratory volume in one second (FEV1); genetic polymorphism; lung function decline