The Journal of allergy and clinical immunology · 2007
TNF polymorphism and bronchoalveolar lavage cell TNF-alpha levels in chronic beryllium disease and beryllium sensitization.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Sato Hiroe, Silveira Lori, Fingerlin Tasha, Dockstader Karen, Gillespie May, Lagan Anna L, Lympany Penny, Sawyer Richard T, du Bois Roland M, Welsh Kenneth I, Maier Lisa A
Аннотация
BACKGROUND: Beryllium stimulates TNF-alpha from chronic beryllium disease (CBD) bronchoalveolar lavage (BAL) cells.
OBJECTIVE: We sought to relate TNF polymorphisms to beryllium-stimulated TNF-alpha production, to the development of CBD, and to the risk of more severe CBD over time.
METHODS: We recruited 147 patients with CBD, 112 beryllium-sensitized subjects, and 323 control subjects; genotyped 5 TNF promoter polymorphisms; and measured beryllium-stimulated and unstimulated BAL cell TNF-alpha production from a subset of subjects.
RESULTS: Beryllium-stimulated, but not beryllium-unstimulated, BAL cell TNF-alpha production was significantly increased in patients with CBD compared with that seen in those only sensitized (P = .0002). Those subjects with the TNF -857T allele and the only haplotype (haplotype 4) containing this allele demonstrated significantly lower unstimulated BAL cell TNF-alpha production compared with that seen in noncarriers (P = .009). Patients with CBD alone and combined with sensitized subjects carrying the TNF haplotype 1 compared with those without this haplotype had significantly increased beryllium-stimulated BAL cell TNF-alpha levels (P = .02). We found no significant association between patients with CBD, sensitized subjects, and control subjects with any of the TNF promoter polymorphisms or haplotypes. A greater decrease in Pao(2) at maximum exercise was noted in patients with CBD with the -1031C allele (P = .03) and with haplotypes other than the TNF haplotype 1 (P = .01), 3 (from 5) of which contain the -1031C allele.
CONCLUSIONS: The -857T allele and haplotype 1 are associated with BAL cell TNF-alpha production, indicating a potential role of TNF promoter variants in regulation of TNF production in sensitized subjects and patients with CBD.
CLINICAL IMPLICATIONS: TNF promoter variants are not risk factors for CBD or sensitization.
OBJECTIVE: We sought to relate TNF polymorphisms to beryllium-stimulated TNF-alpha production, to the development of CBD, and to the risk of more severe CBD over time.
METHODS: We recruited 147 patients with CBD, 112 beryllium-sensitized subjects, and 323 control subjects; genotyped 5 TNF promoter polymorphisms; and measured beryllium-stimulated and unstimulated BAL cell TNF-alpha production from a subset of subjects.
RESULTS: Beryllium-stimulated, but not beryllium-unstimulated, BAL cell TNF-alpha production was significantly increased in patients with CBD compared with that seen in those only sensitized (P = .0002). Those subjects with the TNF -857T allele and the only haplotype (haplotype 4) containing this allele demonstrated significantly lower unstimulated BAL cell TNF-alpha production compared with that seen in noncarriers (P = .009). Patients with CBD alone and combined with sensitized subjects carrying the TNF haplotype 1 compared with those without this haplotype had significantly increased beryllium-stimulated BAL cell TNF-alpha levels (P = .02). We found no significant association between patients with CBD, sensitized subjects, and control subjects with any of the TNF promoter polymorphisms or haplotypes. A greater decrease in Pao(2) at maximum exercise was noted in patients with CBD with the -1031C allele (P = .03) and with haplotypes other than the TNF haplotype 1 (P = .01), 3 (from 5) of which contain the -1031C allele.
CONCLUSIONS: The -857T allele and haplotype 1 are associated with BAL cell TNF-alpha production, indicating a potential role of TNF promoter variants in regulation of TNF production in sensitized subjects and patients with CBD.
CLINICAL IMPLICATIONS: TNF promoter variants are not risk factors for CBD or sensitization.