Mendelian Randomization Study of Interleukin-6 in Chronic Obstructive Pulmonary Disease

<i>Background:</i> 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). <i>Objectives:</i> To investigate the association between IL6 and the risk of COPD using a Mendelian randomization approach. <i>Methods:</i> Eight common single-nucleotide polymorphisms (SNPs) in the region of the <i>IL6 </i>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. <i>Results:</i> 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 <i>IL6 </i>gene and COPD. <i>Conclusions:</i> 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 <i>IL6 </i>gene and the risk of COPD.