13 research outputs found
Susceptibility to chronic mucus hypersecretion, a genome wide association study
Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH
The surface topography of a monogenean,Diclidophora merlangi revealed by scanning electron microscopy
Experimental occlusal interferences. Part III. Mandibular rotations induced by a rigid interference
Prevalence of respiratory disorders among aluminium potroom workers in relation to exposure to fluoride.
Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample.
Experimental occlusal interferences. Part IV. Mandibular rotations induced by a pliable interference
Exploring the Linkage between Awareness and Perception of High-performance Work Practices with Employee Well-being at Workplace: A New Dimension for HRM
Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study
Pathogenesis and treatment of chronic pulmonary disease