TGF-β1 variants in chronic beryllium disease and sarcoidosis

Alexas C. Jonth, Lori Silveira, Tasha E. Fingerlin, Hiroe Sato, Julie C. Luby, Kenneth I. Welsh, Cecile S. Rose, Lee S. Newman, Roland M. Du Bois, Lisa A. Maier, Steven E. Weinberger, Patricia Finn, Erik Garpestad, Allison Moran, Henry Yeager, David L. Rabin, Susan Stein, Michael C. Iannuzzi, Benjamin A. Rybicki, Marcie MajorMary Maliarik, John Popovich, David Moller, Carol J. Johns, Cynthia S Rand, Joanne Steimel, Marc A. Judson, Susan D'Alessandro, Nancy Heister, Theresa Johnson, Daniel T. Lackland, Janardan Pandey, Steven Sahn, Charlie Strange, Alvin S. Teirstein, Louis DePalo, Sheldon Brown, Marvin Lesser, Maria L. Padilla, Marilyn Marshall, Cecile Rose, Juliana Barnard, John Martyny, Charles McCammon, Robert P. Baughman, Elyse E. Lower, Donna B. Winget, Geoffrey McLennan, Gary Hunninghake, Chuck Dayton, Linda Powers, Milton D. Rossman, Eddy A. Bresnitz, Ronald Daniele, Jackie Regovich, William Sexauer, Robert Musson, Joanne Deshler, Paul Sorlie, Margaret Wu, Reuben Cherniack, Lee Newman, Genell L. Knatterud, Michael L. Terrin, Bruce W. Thompson, Kathleen Brown, Margaret Frederick, Frances LoPresti, Patricia Wilkins, Martha Canner, Judy Dotson, Steve Lindenfelser, Mark Cosentino

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Abstract

Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-β1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-β1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-β1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-β1 variants or haplotypes. The -509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the -509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the -509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the -509C and codon 10T, implicated in lower levels of TGF-β1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-β1, although future studies will be needed to correlate TGF-β1 protein levels with known TGF-β1 genotypes and assess whether there is a shared mechanisms for TGF-β1 in these two granulomatous diseases.

Original languageEnglish (US)
Pages (from-to)4255-4262
Number of pages8
JournalJournal of Immunology
Volume179
Issue number6
Publication statusPublished - Sep 15 2007

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ASJC Scopus subject areas

  • Immunology

Cite this

Jonth, A. C., Silveira, L., Fingerlin, T. E., Sato, H., Luby, J. C., Welsh, K. I., ... Cosentino, M. (2007). TGF-β1 variants in chronic beryllium disease and sarcoidosis. Journal of Immunology, 179(6), 4255-4262.