TY - JOUR
T1 - Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis
AU - Nadif, Rachel
AU - Mintz, Margaret
AU - Rivas-Fuentes, Selma
AU - Jedlicka, Anne
AU - Lavergne, Elise
AU - Rodero, Mathieu
AU - Kauffmann, Francine
AU - Combadière, Christophe
AU - Kleeberger, Steven R.
N1 - Funding Information:
We thank the medical staff, specially Dr Jean-Pierre Bertrand and all the French coal mine workers who made this study possible. This research was in part supported by Environment and Health program grant ATC-ASE04080LSA, National Institutes of Health grant ES-09606, and Environmental Protection Agency grant R-825815. Selma Rivas-Fuentes was funded by PAEP-UNAM and CONACYT. Elise Lavergne was recipient of the fellowship from the French Ministry of Research and Technology.
PY - 2006/2/7
Y1 - 2006/2/7
N2 - Chemokines and their receptors are key regulators of inflammation and may participate in the lung fibrotic process. Associations of polymorphisms in CCL5 (G-403A) and its receptor CCR5 (Δ32), CCL2 (A-2578G) and CCR2 (V64I), and CX3CR1 V249I and T280M with coal worker's pneumoconiosis (CWP) were investigated in 209 miners examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score, and CWP prevalence in 1999. CCR5 Δ32 carriers had significantly higher CT score in 1990 and 1994 (2.15 vs. 1.28, p = 0.01; 3.04 vs. 1.80, p = 0.04). The CX3CR1 I249 allele was significantly associated with lower 1990 CT score and lower progression in 4-year change in CT score in CCR5 Δ32 carriers only (p for interaction = 0.03 and 0.02). CX3CR1 V249I was associated with lower 1999 CWP prevalence (16.7%, 13.2%, 0.0% for VV, VI and II); the effect was most evident in miners with high dust exposure (31.6%, 21.7%, 0.0%). Our findings indicate that chemokine receptors CCR5 and CX3CR1 may be involved in the development of pneumoconiosis.
AB - Chemokines and their receptors are key regulators of inflammation and may participate in the lung fibrotic process. Associations of polymorphisms in CCL5 (G-403A) and its receptor CCR5 (Δ32), CCL2 (A-2578G) and CCR2 (V64I), and CX3CR1 V249I and T280M with coal worker's pneumoconiosis (CWP) were investigated in 209 miners examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score, and CWP prevalence in 1999. CCR5 Δ32 carriers had significantly higher CT score in 1990 and 1994 (2.15 vs. 1.28, p = 0.01; 3.04 vs. 1.80, p = 0.04). The CX3CR1 I249 allele was significantly associated with lower 1990 CT score and lower progression in 4-year change in CT score in CCR5 Δ32 carriers only (p for interaction = 0.03 and 0.02). CX3CR1 V249I was associated with lower 1999 CWP prevalence (16.7%, 13.2%, 0.0% for VV, VI and II); the effect was most evident in miners with high dust exposure (31.6%, 21.7%, 0.0%). Our findings indicate that chemokine receptors CCR5 and CX3CR1 may be involved in the development of pneumoconiosis.
KW - Chemokines
KW - Interaction
KW - Occupational exposure
KW - Pneumoconiosis
KW - Polymorphism
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U2 - 10.1016/j.cyto.2006.01.001
DO - 10.1016/j.cyto.2006.01.001
M3 - Article
C2 - 16524739
AN - SCOPUS:33644923223
SN - 1043-4666
VL - 33
SP - 171
EP - 178
JO - Cytokine
JF - Cytokine
IS - 3
ER -