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dc.contributor.authorCho, Michael H.en_US
dc.contributor.authorKlanderman, Barbara J.en_US
dc.contributor.authorLitonjua, Augusto A.en_US
dc.contributor.authorSparrow, Daviden_US
dc.contributor.authorSilverman, Edwin K.en_US
dc.contributor.authorRaby, Benjamin A.en_US
dc.date.accessioned2011-12-29T21:02:23Z
dc.date.available2011-12-29T21:02:23Z
dc.date.copyright2008
dc.date.issued2008-12-30
dc.identifier.citationCho, Michael H, Barbara J Klanderman, Augusto A Litonjua, David Sparrow, Edwin K Silverman, Benjamin A Raby. "Folliculin mutations are not associated with severe COPD" BMC Medical Genetics 9:20. (2008)
dc.identifier.issn1471-2350
dc.identifier.urihttps://hdl.handle.net/2144/2517
dc.description.abstractBACKGROUND: Rare loss-of-function folliculin (FLCN) mutations are the genetic cause of Birt-Hogg-Dubé syndrome, a monogenic disorder characterized by spontaneous pneumothorax, fibrofolliculomas, and kidney tumors. Loss-of-function folliculin mutations have also been described in pedigrees with familial spontaneous pneumothorax. Because the majority of patients with folliculin mutations have radiographic evidence of pulmonary cysts, folliculin has been hypothesized to contribute to the development of emphysema. To determine whether folliculin sequence variants are risk factors for severe COPD, we genotyped seven previously reported Birt-Hogg-Dubé or familial spontaneous pneumothorax associated folliculin mutations in 152 severe COPD probands participating in the Boston Early-Onset COPD Study. We performed bidirectional resequencing of all 14 folliculin exons in a subset of 41 probands and subsequently genotyped four identified variants in an independent sample of345 COPD subjects from the National Emphysema Treatment Trial (cases) and 420 male smokers with normal lung function from the Normative Aging Study (controls). RESULTS: None of the seven previously reported Birt-Hogg-Dubé or familial spontaneous pneumothorax mutations were observed in the 152 severe, early-onset COPD probands. Exon resequencing identified 31 variants, including two non-synonymous polymorphisms and two common non-coding polymorphisms. No significant association was observed for any of these four variants with presence of COPD or emphysema-related phenotypes. CONCLUSION: Genetic variation in folliculin does not appear to be a major risk factor for severe COPD. These data suggest that familial spontaneous pneumothorax and COPD have distinct genetic causes, despite some overlap in radiographic characteristics.en_US
dc.description.sponsorshipNational Institutes of Health (R01 HL075478, R01 HL71393, K08 HL74193, T32 HL07427); National Heart, Lung, and Blood Institute (N01HR76101-N01HR76116, N01HR67118, N01HR76119); Centers for Medicare and Medicaid Services; Agency for Healthcare Research and Quality; Coorperative Studies Program of the US Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center; GlaxoSmithKline; Astra-Zeneca; Wyeth and Bayeren_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2008 Cho et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleFolliculin Mutations Are not Associated with Severe COPDen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1471-2350-9-120
dc.identifier.pmid19116017
dc.identifier.pmcid2636779


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Copyright 2008 Cho et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2008 Cho et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.