Ji Xiaoming, Wang Lijuan, Wu Baiqun, Han Ruhui, Han Lei, Wang Ting, Yang Jingjin, Ni Chunhui
Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210029, China.
Int J Environ Res Public Health. 2015 Oct 30;12(11):13901-12. doi: 10.3390/ijerph121113901.
Coal workers' pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52-0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41-1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series.
煤工尘肺（CWP）与细胞外基质重塑异常以及肺组织中异常的基质金属蛋白酶（MMPs）有关。我们研究了MMP基因启动子中的三种功能多态性（MMP1 rs1799750、MMP2 rs2285053和MMP3 rs522616）与CWP风险的关联。一项病例对照研究共纳入了693例CWP病例和690例对照。采用TaqMan方法进行基因分型分析。在隐性模型下，CWP病例与对照之间MMP3 rs522616的分布存在统计学显著差异（p = 0.047）。在分层分析中，与AA/AG基因型个体相比，MMP3 rs522616 GG基因型个体患CWP的风险明显降低（校正OR = 0.72，95% CI = 0.52 - 0.99），尤其是在不吸烟者亚组中（校正OR = 0.64，95% CI = 0.41 - 1.00）。此外，用酶联免疫吸附测定法测得的对照组血清MMP3蛋白水平显著低于CWP组（p = 0.02）。在正常血清中，rs522616 GG或AG基因型个体的MMP3水平极低于AA基因型携带者（分别为p < 0.05，p < 0.01）。这些发现表明，MMP3 rs522616多态性可能在中国人群CWP的病因中起作用，并且MMP3可能是CWP的潜在诊断生物标志物，需要更多独立研究在不同人群以及更大样本中验证我们的发现。
