Yucesoy B, Vallyathan V, Landsittel D P, Sharp D S, Matheson J, Burleson F, Luster M I
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Am J Ind Med. 2001 Mar;39(3):286-91. doi: 10.1002/1097-0274(200103)39:3<286::aid-ajim1016>3.0.co;2-7.
Silicosis is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Pro-inflammatory cytokines, such as interleukin-1 (IL-1), play a key role in the development of silicosis by regulating mediators which are responsible for lung injury, inflammation, and potentially fibrosis. To study whether functional single nucleotide polymorphisms (SNPs) located in the regulatory elements of genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist (RA) cytokines are associated with silicosis, we examined 318 Caucasian cases confirmed histopathologically with pulmonary silicosis and 163 controls without any apparent inflammation or other pulmonary disease.
Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism technique.
The proportion of the IL-1RA (+ 2018) allele 2 genotype was increased in miners with silicosis (0.27) compared to controls (0.16). The odds of being a case were 2.15 (CI = 1.4-3.3) times higher for subjects with at least one copy of allele 2. No statistically significant differences in the allelic frequencies or genotype distributions for IL-1alpha (+ 4845) or IL-1beta (+ 3953) were found between the control and disease groups.
This is the first report showing an association between the IL-1RA (+ 2018) polymorphism and silicosis, and suggests that this polymorphism may confer increased risk for the development of the disease.
矽肺的特征是纤维化结节性病变，最终发展为进行性肺纤维化。促炎细胞因子，如白细胞介素 -1（IL-1），通过调节负责肺损伤、炎症以及潜在纤维化的介质，在矽肺的发展中起关键作用。为了研究编码IL-1α、IL-1β和IL-1受体拮抗剂（RA）细胞因子的基因调控元件中的功能性单核苷酸多态性（SNP）是否与矽肺相关，我们检查了318例经组织病理学确诊为肺矽肺的白种人病例和163例无任何明显炎症或其他肺部疾病的对照。
采用聚合酶链反应 - 限制性片段长度多态性技术进行基因分型。
与对照组（0.16）相比，矽肺矿工中IL-1RA（+2018）等位基因2基因型的比例增加（0.27）。至少有一个等位基因2拷贝的受试者成为病例的几率比对照组高2.15倍（CI = 1.4 - 3.3）。在对照组和疾病组之间，未发现IL-1α（+4845）或IL-1β（+3953）的等位基因频率或基因型分布存在统计学显著差异。
这是首次报道显示IL-1RA（+2018）多态性与矽肺之间存在关联，并表明这种多态性可能增加疾病发生的风险。
