St. Georg Medical Center, Robert-Koch-Hospital, Leipzig, Germany.
Eur J Med Res. 2009 Dec 7;14 Suppl 4(Suppl 4):210-5. doi: 10.1186/2047-783x-14-s4-210.
As chronic obstructive pulmonary disease (COPD) is known for poor glucocorticoid (GC) response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR) gene might predispose for COPD and/or disease severity.
Three out of about 50 of the most abundant receptor GR gene polymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV) and 106 age matched healthy subjects (mean FEV1 101.8% predicted). These were genotyped: a) for the N363S (Exon 2; 1220 A > G (I)); b) the BCLI restriction fragment length polymorphism (Intron 2; 647 C >G (II)); and c) the ER2223EK (Exon 2; 198, 200 G >A (III)), using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood.
Genotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms. N363S was found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4%) group (controls 60.4%). ER2223EK lacks in any of the study subjects. Further, SNPs did not correlate with COPD severity stage (GOLD), exacerbation rates, and clinical course.
COPD is not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed only these 3 receptor gene polymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence.
由于慢性阻塞性肺疾病（COPD）的糖皮质激素（GC）反应不佳，我们假设糖皮质激素受体（GR）基因的多态性变体可能导致 COPD 和/或疾病严重程度。
在一项病例对照研究中，研究了大约 50 个最丰富的受体 GR 基因多态性中的 3 个，该研究包括 207 例慢性支气管炎或 COPD 患者（平均 FEV1 预测值为 50.5%，GOLD I-IV）和 106 名年龄匹配的健康受试者（平均 FEV1 预测值为 101.8%）。使用 RT-PCR 和 PCR-RFLP 方法，从 EDTA 血液中提取的基因组 DNA 上对这些基因进行了基因分型：a）N363S（外显子 2；1220 A > G（I））；b）BCLI 限制片段长度多态性（内含子 2；647 C > G（II））；c）ER2223EK（外显子 2；198、200 G > A（III））。
在这三个多态性中，COPD 和健康受试者的基因型分布相似。N363S 在健康受试者中的发现率为 0.94%，而在 COPD 患者中的发现率为 0%。BCLI 在对照组中的检出率为 11.3%，在 COPD 患者中的检出率为 15.5%，而 COPD 患者的杂合子频率较低（44.4%）（对照组为 60.4%）。ER2223EK 不存在于任何研究对象中。此外，SNP 与 COPD 严重程度分期（GOLD）、恶化率和临床过程无关。
COPD 与 N363S、BCLI-RFLP 和 ER2223EK 基因多态性无关。由于我们仅分析了这 3 个受体基因多态性，因此该研究不能排除其他 GR 基因变异和关联可能有影响。
