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Approximately 20% of the population-attributable risk for chronic obstructive pulmonary disease (COPD) arises from family history.
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Early hypothesis-driven candidate gene approaches identified several genes contributing to risk for COPD, including components of the protease/antiprotease system and of the antioxidant pathway.
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More recent unbiased genome-wide association studies have gone on to reveal unanticipated genetic factors, for example, polymorphisms within the nicotinic acetyla choline
Genetic Susceptibility
Section snippets
Key points
Unbiased approaches
Until recently, only mutations of the SERPINA1 gene that are responsible for α1-antitrypsin deficiency were unambiguously linked with the development of COPD. However, this disorder accounts for only 1% to 2% of cases of COPD and so other disease-associated alleles must exist. Recent large multinational GWAS have shed much light on this. In addition to validating the involvement of some candidate genes previously suspected of playing a role in the pathogenesis of COPD, these landmark studies
The Extracellular Matrix
Alveolar tissue consists of epithelial cells, capillaries, and extracellular matrix (ECM), the latter comprising a complex network of scaffolding proteins, principally elastin and collagen. The elastin filaments form from tropoelastin monomers that self-assemble into aggregates and then fuse with microfilaments. Multiple covalent cross-links between the lysines in neighboring filaments provide stability. Cutis laxa is a family of autosomal-dominant (OMIM #123700), X-linked (OMIM #304150), and
Summary
Although environmental exposure to smoke remains the preeminent risk factor for developing COPD, the evidence that heredity plays a major role in an individual’s risk is clear. The combination of GWAS and carefully conducted candidate gene approaches is helping to tease out those genetic variants responsible for the familial clustering of this disease, offering both the personalization of individual risk stratification and, more excitingly, the hope for rational therapeutic interventions based
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Cited by (11)
Multi-target natural products as alternatives against oxidative stress in Chronic Obstructive Pulmonary Disease (COPD)
2019, European Journal of Medicinal ChemistryCitation Excerpt :However, as stated before, the main risk factor is cigarette smoking and COPD is prevalent in cigarette smokers [6,7]. Importantly, due to unique genetic differences among individuals, not all smokers go on to develop COPD [57,58]. Among the genetic factors associated to the development of COPD, one of the most well-known are the mutations of the SERPINA1 gene, responsible for α-1 antitrypsin deficiency, a genetic disorder that predisposes to COPD [59–62].
A novel method for in silico identification of regulatory SNPs in human genome
2017, Journal of Theoretical BiologyCitation Excerpt :Single nucleotide polymorphisms (SNPs), which account for the majority of the genetic variants among human individuals, can cause distinct phenotypes, genetic diseases or increased disease susceptibilities (Huang et al., 2015; Marciniak, et al., 2014).
Tuberculosis and lung damage: From epidemiology to pathophysiology
2018, European Respiratory Review
This work was supported by the Medical Research Council (UK), British Lung Foundation, and Diabetes UK. S.J. Marciniak is an MRC Senior Clinical Fellow (G1002610).