MMP-12 基因多态性-82 A 到 G(rs2276109)在波兰 COPD 患者免疫病理学中的作用：一项病例对照研究。
The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.
机构信息
Institute of Physiotherapy, Faculty of Physical Education and Physiotherapy, Opole University of Technology, Proszkowska street 76, 45-758, Opole, Poland.
Second Department of Internal Medicine of Collegium Medicum, Jagiellonian University in Cracow, Skawińska street 8, 31-066, Kraków, Poland.
出版信息
BMC Med Genet. 2019 Jan 18;20(1):19. doi: 10.1186/s12881-019-0751-9.
BACKGROUND
Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles.
METHODS
We analyzed - 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV% and FEV/FVC parameters).
RESULTS
We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ = 9.0331, p = 0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV% and FEV/FVC) and protein level was found.
CONCLUSIONS
We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.
背景
慢性阻塞性肺疾病（COPD）的主要症状是慢性支气管炎和肺气肿，导致肺组织破坏，这是金属蛋白酶（MMPs）与其组织抑制剂活性失衡的结果。MMP-12 被认为是参与 COPD 发病机制的潜在因素。我们研究了 MMP-12 基因启动子区-82A>G 单核苷酸多态性（rs2276109）在波兰人群 COPD 发病中的作用。
方法
我们分析了 335 名吸烟 COPD 患者和 309 名健康个体（包括 110 名吸烟者）中 MMP-12 基因启动子区-82A>G SNP（rs2276109），此外，60 名 COPD 患者和 61 名对照者（23 名吸烟者）用 ELISA 检测 MMP-12 血清水平。所有受试者均用肺功能仪（FEV%和 FEV/FVC 参数）进行肺功能分析。
结果
我们发现 SNP rs2276109 的-82G 等位基因和-82GG 纯合基因型频率在 COPD 患者中明显低于对照组（分别为 12.5%和 16.9%；χ²=4.742，p=0.02；等位基因和 0.5%和 3.9%，分别；χ²=9.0331，p=0.01；基因型）。此外，-82G 等位基因在对照组吸烟者中比非吸烟者更常见（22.3%比 14.1%；χ²=6.7588，p=0.01）。与对照组相比，COPD 患者的 MMP-12 血清水平明显升高（分别为 6.8ng/ml 和 3.3ng/ml；F=7.433，p<0.0001），尽管独立于分析的基因多态性。此外，肺功能（FEV%和 FEV/FVC）参数与蛋白水平之间无相关性。
结论
我们发现 SNP rs2276109 的-82G 等位基因与 COPD 发病风险降低有关，COPD 患者释放的 MMP-12 多于健康个体，但与该 SNP 无关。
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