Mendelian randomization study of interleukin-6 in chronic obstructive pulmonary disease.

BACKGROUND 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). OBJECTIVES To investigate the association between IL6 and the risk of COPD using a Mendelian randomization approach. METHODS 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. RESULTS 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. CONCLUSIONS 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.