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. 2006 Feb 7;33(3):171-8.
doi: 10.1016/j.cyto.2006.01.001.

Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis

Rachel Nadif  1 , Margaret Mintz, Selma Rivas-Fuentes, Anne Jedlicka, Elise Lavergne, Mathieu Rodero, Francine Kauffmann, Christophe Combadière, Steven R Kleeberger
Affiliations

Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis

Rachel Nadif et al. Cytokine. .

Abstract

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 (Delta32), 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 Delta32 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 Delta32 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.

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Figures

Figure 1
Figure 1. Association of CX3CR1 polymorphisms with pneumoconiosis prevalence according to cumulative occupational exposure in 1999
Cumulative coal dust exposure: low: ≤71 mg/m3 x year, high: >71 mg/m3 x year based on job history and ambient measurements in the coal mine. Numbers of miners in each group are shown below each bar. CWP: coal workers’ pneumoconiosis.
Figure 2
Figure 2. Association of CCR5 Δ32 polymorphism with 1990 (a) and difference between 1990 and 1994 (b) CT scan score according to CCL5 –403 genotypes
Numbers of miners in each group are shown below each bar. CT: computed tomography. (a) Multivariate linear regression model showed that only CCR5 Δ32 was significantly associated with CT score (p = 0.01, p = 0.3 for CCL5 G–403A). (b) Multivariate linear regression model: p =0.15 for CCR5 Δ32 and p = 0.16 for CCL5 G–403A.
Figure 3
Figure 3. Associations of CX3CR1 V249I polymorphism with 1990 (a) and difference between 1990 and 1994 (b) CT scan score according to CCR5 Δ32 genotypes
Numbers of miners in each group are shown below each bar. CT: computed tomography. * p<0.10, ** p<0.05.
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