Robert H. Hollis Laboratory of Environmental and Occupational Health, Division of Environmental and Occupational Health Sciences, Dept of Medicine, National Jewish Medical Health, 1400 Jackson Street, Denver, CO 80206, USA.
Eur Respir J. 2010 Aug;36(2):331-8. doi: 10.1183/09031936.00107809. Epub 2010 Jan 14.
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.
CC 趋化因子受体 5（CCR5）表达于 1 型辅助性 T 细胞，该细胞参与肉芽肿性肺疾病——铍病（CBD）的发病机制。CCR5 基因（CCR5）多态性与结节病的严重程度相关。本研究探讨了 CCR5 多态性与 CBD 及其疾病进展之间的相关性。采用聚合酶链反应-序列特异性引物方法，对 88 例 CBD 患者、86 例铍致敏（BeS）患者和 173 例铍暴露无疾病对照者的 CCR5 多态性进行基因分型。对基因型与肺功能和支气管肺泡灌洗数据进行了相关性分析。在 CBD、BeS 个体和对照组中，基因型和等位基因频率均无显著差异。在 CBD 患者中，发现与 1 秒用力呼气容积和用力肺活量下降以及 CCR5-3458 胸腺嘧啶（T）T 基因型相关（p＜0.0001），与静息时和最大运动时肺泡-动脉氧分压差增加相关（p=0.003 和 p=0.01），与 CCR5-5663 腺嘌呤等位基因相关。在 CBD 和 BeS 联合组中，支气管肺泡灌洗液淋巴细胞计数增加与 CCR5-2459 鸟嘌呤/-2135T 相关（p=0.01）。这是首个显示 CCR5 多态性与 CBD 患者肺功能随时间恶化相关的研究，提示 CCR5 对 CBD 患者肺功能的进展很重要。进一步的研究将有助于阐明 CCR5 多态性影响 CBD 进展的机制。
