Sorbonne Paris nord University, 93430 Villetaneuse, France; INSERM, UMRS1148, CHU X.Bichat, Paris, France; Institut supérieur de biotechnologies de Monastir, University of Monastir, Tunisia; UR12ES06, Physiologie de l'exercice et physiopathologie: de l'intégré au moléculaire, Faculté de médecine de Sousse, University of Sousse, Tunisia.
Sorbonne Paris nord University, 93430 Villetaneuse, France; INSERM, UMRS1148, CHU X.Bichat, Paris, France.
Prostaglandins Leukot Essent Fatty Acids. 2021 Mar;166:102252. doi: 10.1016/j.plefa.2021.102252. Epub 2021 Jan 28.
We hypothesized that polymorphisms of genes involved in the prostaglandin pathway could be associated with COPD. In this study we explored the involvement of genetic polymorphisms in PTGS2, PTGER2 and PTGER4 genes in the development and severity of COPD and their effects on plasma concentrations of inflammatory/oxidative stress markers. We identified genotypes of PTGS2, PTGER2 and PTGER4 SNPs in a Tunisian cohort including COPD patients (n = 138) and control subjects (n = 216) using PCR-RFLP and PCR TaqMan. Pulmonary function (FEV1 and FVC) were assessed by plethsmography. PGE, PGD and cytokine plasma (IL-6, IL-18, TNF-α, TGF-β) concentrations were measured using ELISA and colorimetric standard methods were used to determine oxidative stress concentrations. Genotype frequencies of rs2745557 in PTGS2 and rs2075797 in PTGER2 were different between COPD cases and controls. There was no correlation between these polymorphisms and lung function parameters. For rs2745557, the A allele frequency was higher in COPD cases than in controls. For rs2075797, carriers of the GG genotype were more frequent in the COPD group than in controls. Only rs2745557 in PTGS2 had an effect on PGD and cytokine plasma concentrations. PGD was significantly decreased in COPD patients with the GA or AA genotypes. In contrast, IL-18 and NO plasma concentrations were increased in COPD rs2745557 A allele carriers as compared to homozygous GG subjects. Our findings suggest that rs2745557 in PTGS2 and rs2075797 in PTGER2 are associated with COPD development but not with its severity.
我们假设参与前列腺素途径的基因多态性可能与 COPD 有关。在这项研究中，我们探讨了 PTGS2、PTGER2 和 PTGER4 基因的遗传多态性在 COPD 的发展和严重程度中的作用及其对炎症/氧化应激标志物血浆浓度的影响。我们使用 PCR-RFLP 和 PCR TaqMan 在一个包括 COPD 患者（n=138）和对照受试者（n=216）的突尼斯队列中鉴定了 PTGS2、PTGER2 和 PTGER4 SNPs 的基因型。通过体描法评估肺功能（FEV1 和 FVC）。使用 ELISA 测量 PGE、PGD 和细胞因子（IL-6、IL-18、TNF-α、TGF-β）的血浆浓度，并使用比色标准方法测定氧化应激浓度。PTGS2 中的 rs2745557 和 PTGER2 中的 rs2075797 基因型频率在 COPD 病例和对照之间存在差异。这些多态性与肺功能参数之间没有相关性。对于 rs2745557，COPD 病例中的 A 等位基因频率高于对照组。对于 rs2075797，COPD 组中 GG 基因型的携带者比对照组更频繁。只有 PTGS2 中的 rs2745557 对 PGD 和细胞因子血浆浓度有影响。PGD 在具有 GA 或 AA 基因型的 COPD 患者中显著降低。相反，与纯合 GG 受试者相比，COPD rs2745557 A 等位基因携带者的 IL-18 和 NO 血浆浓度增加。我们的研究结果表明，PTGS2 中的 rs2745557 和 PTGER2 中的 rs2075797 与 COPD 的发生有关，但与严重程度无关。
