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Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

ABSTRACT: 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.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.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).No single marker was significantly associated with either rate of lung function decline or serum CRP levels.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4680456 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

Wang Yu Y Shumansky Karey K Sin Don D DD Man S F Paul SF Akhabir Loubna L Connett John E JE Anthonisen Nicholas R NR Paré Peter D PD Sandford Andrew J AJ He Jian-Qing JQ

International journal of clinical and experimental pathology 20151001 10

<h4>Objective</h4>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.<h4>Methods</h4>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 slowes ...[more]

PMID: 26722511

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Project description:Background Asthma and chronic obstructive pulmonary disease (COPD) are heterogenetic diseases and exhibit many similarities. Dutch hypothesis proposed that these two diseases may have common genetic origins. This study aims to investigate whether asthma and COPD share a common genetic background in Chinese patients. Methods In this case-control study, single nucleotide polymorphisms (SNPs) were genotyped using SNaPshot. Haplotype disease analysis and haplotype phenotype analysis were applied to assess the relationship between three polymorphisms of the FCER2 gene and the risk of COPD/asthma. Additionally, associations between polymorphisms of the FCER2 gene and phenotypes were analyzed. Results We detected ten SNPs of seven genes (FCER1A, FCGR2A, FCGR2B, CHI3L1, ADRB2, STAT6, and FCER2) expressed by airway epithelial cells. We detected genotypes and allele distributions in 251 COPD patients, 597 asthma patients, and 632 healthy controls. A significant difference was found in the FCER2 gene (rs28364072) between COPD patients and controls (P=0.009). Significant differences were observed in the genotype and allele distributions of rs1801274 (FCGR2A), rs12368672 (STAT6), and rs2228137 (FCER2) between asthma patients and controls (P=0.004, 0.007 and 0.010, respectively). Notably, polymorphisms of FCER2 gene were associated with the risk of both COPD (P=0.009 for rs28364072) and asthma (P=0.01 for rs2228137). Haplotype analysis revealed that haplotype T-G-T (alleles of rs28364072, rs2228137, and rs3760687, respectively) was significantly associated with a higher risk of asthma [odds ratios (OR) =2.25, 95% confidence interval (CI): 1.26–4.01, P=0.006]. Further analysis showed that the C-A-C haplotype and C-G-T haplotype were associated with increased blood eosinophils in either COPD or asthma patients (P=0.034, and P<0.001, respectively). Moreover, haplotypes C-A-C, C-G-C, and T-G-C showed significant associations with serum IgE levels in asthma patients (P=0.002, 0.041, and 0.004, respectively). Conclusions Our data suggest that the FCER2 gene might associate with predisposition to asthma and COPD, while FCER2 haplotypes were associated with pulmonary function measurements and blood eosinophils counts in both diseases. Our findings support the common genetic basis for asthma and COPD, suggesting a potential therapeutic target for the two diseases.

Dataset Information

Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

Publications

Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.

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