Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution

Jiang

et al. 2017

COPD

Quantitative computed tomography (CT) measures of emphysema have been shown to be associated with increased mortality in humans, but genetic variants affecting the quantitative parameters of chest CT that measure degree of emphysema have not yet been examined. In this study, using available chest CT data from a total of 344 emphysema patients, we assessed the correlations between five chronic obstructive pulmonary disease (COPD) susceptibility variants in the cholinergic receptor nicotinic (CHRN) genes and the degree of emphysema and chest CT manifestations. We verified that most of the parameters were significantly correlated with the degree of emphysema. Compared to rs76071148AA and TT genotype carriers, the rs76071148AT genotype carriers exhibited a decreased probability of having severe emphysema (odds ratio [OR] =0.63, 95% confidence interval [CI] =0.40–0.99), whereas the variant rs8040868C allele was negatively correlated with the emphysema index (P=0.002). Interestingly, further stratification analysis grouped by spirometry-diagnosed COPD status revealed that the variant rs8040868C (CT + CC) genotypes exerted a protective effect against severe emphysema with borderline significance (OR =0.41, 95% CI =0.16–1.05) and affected the mean lung density, emphysema index, ratio of airway wall thickness to airway dimensions (AWT/AD), and AWT grade in spirometry-diagnosed non-COPD subjects. The rs76071148 variant was also significantly associated with AWT/AD and AWT grade in those individuals. In summary, we determined that rs8040868 and rs76071148 are promising indicators of the degree of emphysema and chest CT manifestations, especially in spirometry-diagnosed non-COPD subjects.

Section: Discussionmentioning

confidence: 61%

“…To date, multiple association studies, especially genome-wide association studies (GWAS), have discovered several genetic loci for emphysema and airway quantitative imaging phenotypes in different ethnicities 17,22,23. Accordantly, these previously reported loci for emphysema are also associated with COPD.…”

Section: Discussionmentioning

confidence: 94%

Two <em>CHRN </em>susceptibility variants for COPD are genetic determinants of emphysema and chest computed tomography manifestations in Chinese patients

Jiang

et al. 2017

COPD

“…This may be helpful in distinguishing COPD form AATD. Genetic determinates may be a possible explanation for the untypical high emphysema scores in the basal lung regions in the COPD group, but at the present time, this cannot be proven [9]. Furthermore, COPD had significantly higher overall emphysema score and showed more severe types of emphysema.…”

Section: Discussionmentioning

confidence: 64%

“…Furthermore, there may be unique genetic differences among individuals leading to greater susceptibility to the adverse effects of cigarette smoke [7]. Genetic factors have subsequently been attributed to specific patterns and distribution of emphysema [8,9]. AATD and COPD share morphological features of emphysematous destruction of lung parenchyma and airway changes on CT.…”

Section: Introductionmentioning

confidence: 99%

Similarities in the Computed Tomography Appearance in α1-Antitrypsin Deficiency and Smoking-Related Chronic Obstructive Pulmonary Disease in a Smoking Collective

et al. 2018

Background: Emphysematous destruction of lung parenchyma visible in computed tomography (CT) can be attributed to chronic obstructive pulmonary disease (COPD) or to α1-antitrypsin deficiency (AATD). Objectives: We evaluated if visual semiquantitative phenotyping of CT data helps identifying individuals with AATD in a group of smokers with severe emphysema and airflow limitation. Method: n = 14 patients with AATD and n = 15 with COPD and a minimum of 10 pack years underwent CT, clinical assessment, and full-body plethysmography. The extent and type of emphysema as well as large and small airway changes were rated semiquantitatively for each lobe using a standardized previously published scoring system. Lastly, a final diagnosis for each patient was proposed. Results: AATD had a significantly lower mean emphysema score than COPD, with 8.9 ± 3.4 versus 11.9 ± 3.2 (p < 0.001), respectively. Within both groups, there was significantly more emphysema in the lower lobes (p < 0.05–0.001). The COPD group showed an upper- and middle-lobe predominance of emphysema distribution when compared to the AATD group (p < 0.001). Centrilobular (CLE) and panlobular (PLE) emphysema patterns showed a uniform distribution within both groups, with a CLE predominance in the upper lung and a PLE predominance in the lower lung regions. AATD and COPD both showed significantly more airway changes in lower lobes compared to upper lobes (p = 0.05–0.001), without significant differences between both groups. Conclusion: The typical emphysema distribution patterns seen on CT traditionally assigned to AATD and COPD were of little use in discriminating both entities. Also, airway changes could not contribute to a more precise differentiation. We conclude that a concise standardized phenotyping-driven approach to chest CT in emphysema is not sufficient to identify patients with AATD in a cohort of smokers with advanced emphysema.

“…Genome-wide meta-analysis of emphysema by Boueiz A et al showed that multicohort genome-wide association study (GWAS) of emphysema distribution has identified five significant loci 1. It has been previously confirmed that 4q31 near hedgehog interacting protein (HHIP) and 15q25 near cholinergic receptor nicotinic alpha 5 subunit (CHRNA5) are associated with susceptibility to COPD driven by smoking behavior, whereas 4q13 near SHOWAHB, 8q24 near trafficking protein particle complex 9 (TRAPPC9) and 10p12 near KIAA1462 are newly identified genes, associated with susceptibility to COPD.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism and chronic obstructive pulmonary disease

Yuan¹,

Chang

Gao

et al. 2017

COPD

Chronic obstructive pulmonary disease (COPD) is a common chronic disease, and its morbidity and mortality are increasing. There are many studies that have tried to explain the pathogenesis of COPD from genetic susceptibility, to identify the susceptibility of COPD factors, which play a role in early prevention, early detection and the early treatment. However, it is well known that COPD is an inflammatory disease characterized by incomplete reversible airflow limitation in which genes interact with the environment. In recent years, many studies have proved gene polymorphisms and COPD correlation. However, there is less research on the relationship between COPD and genome-wide association study (GWAS), epigenetics and apoptosis. In this paper, we summarized the correlation between gene level and COPD from the following four aspects: the GWAS, the gene polymorphism, the epigenetics and the apoptosis, and the relationship between COPD and gene is summarized comprehensively.