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CC chemokine receptor 5 gene polymorphisms in beryllium disease.

Authors: Sato, H  Silveira, L  Spagnolo, P  Gillespie, M  Gottschall, EB  Welsh, KI  Du Bois, RM  Newman, LS  Maier, LA 
Citation: Sato H, etal., Eur Respir J. 2010 Aug;36(2):331-8. Epub 2010 Jan 14.
Pubmed: (View Article at PubMed) PMID:20075058
DOI: Full-text: DOI:10.1183/09031936.00107809

CC chemokine receptor 5 (CCR5) is expressed on type-1 T-helper cells, which are involved in the pathogenesis of the granulomatous lung disease chronic beryllium disease (CBD). CCR5 gene (CCR5) polymorphisms are associated with sarcoidosis severity. The present study explores associations between CCR5 polymorphisms and CBD and its disease progression. Eight CCR5 polymorphisms were genotyped in CBD (n = 88), beryllium sensitisation (BeS; n = 86) and beryllium-exposed nondiseased controls (n = 173) using PCR with sequence-specific primers. Pulmonary function and bronchoalveolar lavage data were examined for associations with genotypes. There were no significant differences in genotype and allele frequency between CBD, BeS individuals and controls. In CBD, associations were found with decline in forced expiratory volume in 1 s and forced vital capacity and the CCR5 -3458 thymidine (T)T genotype (p<0.0001), and an increase in alveolar-arterial oxygen tension difference at rest (p = 0.003) and at maximum exercise (p = 0.01) and the -5663 adenine allele. Increased bronchoalveolar lavage lymphocyte numbers were associated with CCR5 -2459 guanine/-2135T (p = 0.01) only in the combined CBD and BeS group. This is the first study showing that CCR5 polymorphisms are associated with worsening pulmonary function over time in CBD, suggesting that CCR5 is important in the progression of pulmonary function in CBD. Further studies would be useful to clarify the mechanism whereby CCR5 polymorphisms affect progression of CBD.

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RGD Object Information
RGD ID: 4892065
Created: 2011-02-01
Species: All species
Last Modified: 2011-02-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.