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Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations.

ABSTRACT: Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qualitative COPD-related phenotypes were found for the tumor necrosis factor (TNF)-alpha -308G>A promoter polymorphism (P < 0.02), a coding variant in surfactant protein B (SFTPB Thr131Ile) (P = 0.03), and the (GT)(31) allele of the heme oxygenase (HMOX1) promoter short tandem repeat (P = 0.02). In the case-control study, the SFTPB Thr131Ile polymorphism was associated with COPD, but only in the presence of a gene-by-environment interaction term (P = 0.01 for both main effect and interaction). The 30-repeat, but not the 31-repeat, allele of HMOX1 was associated (P = 0.04). The TNF -308G>A polymorphism was not significant. In addition, the microsomal epoxide hydrolase "fast" allele (EPHX1 His139Arg) was significantly associated in the case-control study (P = 0.03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs.

SUBMITTER: Hersh CP

PROVIDER: S-EPMC2715305 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations.

Hersh Craig P CP Demeo Dawn L DL Lange Christoph C Litonjua Augusto A AA Reilly John J JJ Kwiatkowski David D Laird Nan N Sylvia Jody S JS Sparrow David D Speizer Frank E FE Weiss Scott T ST Silverman Edwin K EK

American journal of respiratory cell and molecular biology 20050407 1

Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qu ...[more]

PMID: 15817713

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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.

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Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations.

Publications

Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations.

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