Year: 2006
Type: article
Study design: Observational Study
Abstract: Genome-wide linkage analysis in the Boston Early-Onset Chronic Obstructive Pulmonary Disease (COPD) Study has demonstrated significant evidence of linkage to chromosome 8p for forced expiratory volume in 1 second, an important COPD-related phenotype. In this study, we sought to fine map the linkage peak and to test variants in two candidate genes for association with COPD and related traits. In a variance component linkage analysis on chromosome 8, including seven additional short tandem repeat markers, the logarithm of the odds of linkage score was reduced from 3.30 to 1.80 (at 1 cM). Five single nucleotide polymorphisms (SNPs) in Defensin Beta-1 (DEFB1) were genotyped in the Boston Early-Onset COPD Study families; none was significantly associated. Four SNPs and an insertion-deletion polymorphism in Macrophage Scavenger Receptor-1 (MSR1) were also genotyped in the family-based study. A coding variant (Pro275Ala) was marginally associated with two qualitative airflow obstruction traits (p < or = 0.02). This SNP showed a trend toward association in a case-control study comparing participants in the National Emphysema Treatment Trial to smoker controls (p = 0.07). Despite the reduced support for linkage upon further analysis, it remains possible that chromosome 8p contains a gene that influences COPD susceptibility. There is marginal, though not convincing, evidence for association with MSR1.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G1207659464, G1220799682, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, G1439225947, G1576662596, G1615620936, CLINICAL CENTER FOR LVRS, G1735610881, CLNICAL CENTER FOR LVRS, CLNICAL CENTER FOR LVRS, Fine Mapping of a COPD Locus on Chromosome 19q, G182694510, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2412257637, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2599011918, G278468722, G3110798224, CLINICAL COORDINATING CENTER FOR LVRS, G3805264881, G3985801443, G4153249725, G4255341634, Genetics of COPD in NETT, G4731985522, Fine Mapping of COPD Susceptibility Genes, G48533833, G4899389735, G5332233980, G556935766, G6315211796, CLNICAL CENTER FOR THE LVRS, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR LVRS, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G778147052, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY
OpenAlex ID: W2115449634