Department of Respiratory Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Respiration. 2011;82(6):530-8. doi: 10.1159/000332336. Epub 2011 Oct 11.
Cross-sectional studies have demonstrated that increased levels of interleukin-6 (IL6) are present in the airways and blood samples of patients with chronic obstructive pulmonary disease (COPD).
To investigate the association between IL6 and the risk of COPD using a Mendelian randomization approach.
Eight common single-nucleotide polymorphisms (SNPs) in the region of the IL6 gene were genotyped using both TaqMan and Illumina in the Rotterdam Study, a prospective population-based cohort study consisting of 7,983 participants aged 55 years or older, including 928 COPD patients. At baseline, blood was drawn in a random sample of 714 subjects to measure the IL6 plasma level. Analysis of variance, logistic regression, and Cox proportional hazard models--adjusted for age, gender, pack years, and BMI--were used for analyses.
High levels of IL6 (>2.4 pg/ml, the highest tertile) were associated with a three-fold increased risk of developing COPD, in comparison to low levels (<1.4 pg/ml, the lowest tertile). The rs2056576 SNP was associated with a 10% increase in the risk of COPD per additional T allele. However, the association was no longer significant after adjustment. No association was found with other common SNPs in the IL6 gene and COPD.
Although increased IL6 plasma levels at baseline are associated with the risk of developing COPD during follow-up, there was no strong evidence for an association between common variation in the IL6 gene and the risk of COPD.
横断面研究表明，慢性阻塞性肺疾病（COPD）患者的气道和血液样本中白细胞介素-6（IL6）水平升高。
采用孟德尔随机化方法研究 IL6 与 COPD 风险之间的关联。
在 Rotterdam 研究中，使用 TaqMan 和 Illumina 对 IL6 基因区域的 8 个常见单核苷酸多态性（SNP）进行基因分型。该前瞻性基于人群的队列研究包括 7983 名年龄在 55 岁或以上的参与者，其中包括 928 名 COPD 患者。在基线时，从 714 名随机抽取的受试者中抽取血液以测量 IL6 血浆水平。采用方差分析、逻辑回归和 Cox 比例风险模型进行分析，调整因素包括年龄、性别、吸烟包年数和 BMI。
与低水平（<1.4pg/ml，最低三分位）相比，高水平（>2.4pg/ml，最高三分位）的 IL6 与发展为 COPD 的风险增加三倍相关。rs2056576 SNP 与 COPD 风险增加 10%相关，每增加一个 T 等位基因。然而，调整后这种关联不再显著。IL6 基因中的其他常见 SNP 与 COPD 之间没有关联。
虽然基线时 IL6 血浆水平升高与随访期间发生 COPD 的风险相关，但 IL6 基因常见变异与 COPD 风险之间没有强有力的证据。
