TGF-beta 1 variants in chronic beryllium disease and sarcoidosis.
Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-beta1, 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-beta1 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-beta1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-beta1 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-beta1 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-beta1, although future studies will be needed to correlate TGF-beta1 protein levels with known TGF-beta1 genotypes and assess whether there is a shared mechanisms for TGF-beta1 in these two granulomatous diseases.
Jonth
Alexas C
AC
Robert H. Hollis Laboratory of Environmental and Occupational Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Silveira
Lori
L
Fingerlin
Tasha E
TE
Sato
Hiroe
H
Luby
Julie C
JC
Welsh
Kenneth I
KI
Rose
Cecile S
CS
Newman
Lee S
LS
du Bois
Roland M
RM
Maier
Lisa A
LA
D000328:Adult; D001607:Berylliosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D001608:Beryllium / Q000009:adverse effects; D016022:Case-Control Studies; D002908:Chronic Disease; D003062:Codon / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012507:Sarcoidosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics*