Chronic obstructive pulmonary disease * 1: Susceptibility factors for COPD the genotype-environment interaction

Sandford, Andrew J.; Silverman, EK

doi:10.1136/thorax.57.8.736

Cited by 137 publications

(107 citation statements)

References 87 publications

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“…This suggests that a combination of genetic and environmental factors interact to cause COPD, and there has been much research aiming to identify candidate genes that may confer genetic susceptibility. To date, however, only deficiency alleles on the 1AT gene have been robustly identified as predisposing to disease (9). Pathologically, COPD is characterised by widespread inflammation of the peripheral and central airways with destruction of the lung parenchyma.…”

Section: Introductionmentioning

confidence: 99%

The Importance of Chronic Bronchitis in Chronic Obstructive Pulmonary Disease

Sapey¹,

Stockley²

2011

Bronchitis

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Section: Introductionmentioning

confidence: 99%

The Importance of Chronic Bronchitis in Chronic Obstructive Pulmonary Disease

Sapey¹,

Stockley²

2011

Bronchitis

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“…However, the lung disease phenotype caused by CS exposure is variable, suggesting that other factors can modify disease expression, including genetic and environmental factors (10)(11)(12)(13)(14). Alpha-1 antitrypsin deficiency has been shown to increase the risk of COPD in early adulthood, and CS exposure can hasten disease onset in these individuals (15). Alternatively, genetic polymorphisms in the promoter sequence of MMP-12 have been shown to reduce the risk of COPD in adults that smoke (16).…”

mentioning

confidence: 99%

Neonatal Hyperoxia Contributes Additively to Cigarette Smoke–Induced Chronic Obstructive Pulmonary Disease Changes in Adult Mice

McGrath‐Morrow¹,

Lauer²,

Collaco³

et al. 2011

Am J Respir Cell Mol Biol

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The extent by which early postnatal lung injury contributes to the development of chronic obstructive pulmonary disease (COPD) in the adult is unclear. We hypothesized that exposure to hyperoxia during early postnatal life can augment lung changes caused by adult chronic cigarette smoke (CS) exposure. C57BL/6J mice (1 d old) were exposed to hyperoxia (O 2 ) for 5 days. At 1 month of age, half of the O 2 -exposed mice and half of the control mice were placed in a CS chamber for 6 months. After exposure to CS, mice underwent quasistatic pressure-volume curve and mean chord length measurements; quantification of pro-Sp-c expression; and measurement of lung IL-8/ KC, CXCR2/IL8Ra, TNF-a, and IL-6 mRNA by real-time PCR. Adult mice exposed to O 2 1CS had significantly larger chord length measurements (P , 0.02) and lung volumes at 35 cm H 2 O (P , 0.05) compared with all other groups. They also had significantly less proSp-c protein and surfactant protein C mRNA expression (P , 0.003). Mice exposed to O 2 1CS and CS-only mice had significantly higher lung resistance and longer mean time constants (P , 0.01), significantly more inflammatory cells in the bronchoalveolar lavage fluid (P , 0.03), and significantly higher levels of lung CXCR2/IL8Ra mRNA compared with mice not exposed to smoke (P , 0.02). We conclude that exposure to early postnatal hyperoxia contributed additively to CS-induced COPD changes in adult mice. These results may be relevant to a growing population of preterm children who sustained lung injury in the newborn period and may be exposed to CS in later life.

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“…Cigarette smoking is the most important environmental risk factor for the development of COPD (Sandford & Silverman 2002;Celli et al 2004). Nevertheless, despite its recognized importance only 20-30% of smokers develop symptomatic COPD (Lokke et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…packyears and duration of smoking, account for only about 15% of the variation in lung function decline in smokers (Beck et al 1981). Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies indicate that COPD is a genetically complex disease with environmental factors and many involved genes interacting together (Silverman et al 1998;Sandford & Silverman 2002). Such interactions are defined by a non-additive contribution of each gene and environmental factor to the overall phenotype, thus confering a different level of risk than expected by simply adding them (Sandford & Silverman 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Severe α 1 -antitrypsin deficiency with a simple Mendelian inheritance and related more common genetic variants of this serine protease-inhibitor that confer the susceptibility to the disease have been thoroughly reviewed elsewhere (Joos et al 2002b;Sandford & Silverman 2002). In this review we attempt to summarize the up-to-date knowledge about other gene polymorphisms that have been linked to the risk of developing COPD and/or may account for variations in the disease course.…”

Section: Introductionmentioning

confidence: 99%

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The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

et al. 2008

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20-30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

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Chronic obstructive pulmonary disease * 1: Susceptibility factors for COPD the genotype-environment interaction

Cited by 137 publications

References 87 publications

The Importance of Chronic Bronchitis in Chronic Obstructive Pulmonary Disease

The Importance of Chronic Bronchitis in Chronic Obstructive Pulmonary Disease

Neonatal Hyperoxia Contributes Additively to Cigarette Smoke–Induced Chronic Obstructive Pulmonary Disease Changes in Adult Mice

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

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