Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

DeMeo, Dawn L.; Celedón, Juan C.; Lange, Christoph; Reilly, John J.; Chapman, Harold A.; Sylvia, Jody S.; Speizer, Frank E.; Weiss, Scott T.; Silverman, Edwin K.

doi:10.1164/rccm.200404-524oc

Cited by 59 publications

(53 citation statements)

References 33 publications

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“…Since FEV1 (% pred) was studied in only four asthma genome screens, linkage scans conducted for lung function phenotypes in families with early-onset chronic obstructive pulmonary disease (COPD) and from the general population were considered [24]. Among the three linkage signals detected for FEV1, 1p36 was reported to be linked to asthma in two scans [22,25] and 6q14 to eosinophils in one scan [26], whereas linkage to 2q36 was observed for atopy phenotypes in two asthma scans [18,21,22] and for lung function phenotypes in asthmatic families [19] and early-onset COPD families [27,28]. Regarding this latter result, longitudinal studies have shown that asthma is associated with accelerated lung function decline and is a risk factor for COPD [29].…”

Section: Phenotype Definition and Linkage Analysis Outcomesmentioning

confidence: 99%

Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families

Siroux¹,

Dizier²,

Lemainque³

et al. 2007

Eur Respir J

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There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes.A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n5508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV1) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum).This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV1. Moreover, FEV1 appeared to have no genetic determinant in common with asthma severity and asthma scores.Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.

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Section: Phenotype Definition and Linkage Analysis Outcomesmentioning

confidence: 99%

Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families

Siroux¹,

Dizier²,

Lemainque³

et al. 2007

Eur Respir J

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“…7 In fact, the IL8RA region on chromosome 2q showed significant linkage to the FEV 1 /FVC ratio in a genomewide screen of COPD families. 32,33 The same region showed evidence for linkage to total serum IgE levels in patients with asthma. 16 Associations of total serum IgE levels with asthma and bronchial hyper-responsivness have been demonstrated.…”

Section: Segmentmentioning

confidence: 92%

Association of interleukin-8 receptor α polymorphisms with chronic obstructive pulmonary disease and asthma

et al. 2005

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Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptor a (IL8RA, CXCR1) and b (IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P ¼ 0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.

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“…The region of tightest linkage was at the 6q terminus, just beyond the lung cancer linkage region and extending to the end of the chromosome. Evidence for linkage of lung function to moderate obstructive lung disease in smokers was reported on chromosome 12p (35,36), and quantitative measures of FEV 1 and FVC have been linked to a region on 2q36 (37). The phenotype of postbronchodilator FEV 1 in these families was linked to a region on 8p23.…”

Section: Family Linkage Studiesmentioning

confidence: 96%

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

Schwartz

2012

Proc Am Thorac Soc

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Chronic obstructive pulmonary disease (COPD) and lung cancer represent two diseases that share a strong risk factor in smoking, and COPD increases risk of lung cancer even after adjusting for the effects of smoking. These diseases not only occur jointly within an individual but also there is evidence of shared occurrence within families. Understanding the genetic contributions to these diseases, both individually and jointly, is needed to identify the highest risk group for screening and targeted prevention, as well as aiding in the development of targeted treatments. The chromosomal regions that have been identified as being associated either jointly or independently with lung cancer, COPD, nicotine addiction, and lung function are presented. Studies jointly measuring genetic variation in lung cancer and COPD have been limited by the lack of detailed COPD diagnosis and severity data in lung cancer populations, the lack of lung cancer-specific phenotypes (histology and tumor markers) in COPD populations, and the lack of inclusion of minorities. African Americans, who smoke fewer cigarettes per day and have different linkage disequilibrium and disease patterns than whites, and Asians, also with different patterns of exposure to lung carcinogens and linkage patterns, will provide invaluable information to better understand shared and independent genetic contributions to lung cancer and COPD to more fully define the highest risk group of individuals who will most benefit from screening and to develop molecular signatures to aid in targeted treatment and prevention efforts.

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Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

Cited by 59 publications

References 33 publications

Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families

Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families

Association of interleukin-8 receptor α polymorphisms with chronic obstructive pulmonary disease and asthma

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

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