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000332336_sm_Suppl._Material.doc (75.5 kB)

Supplementary Material for: Mendelian Randomization Study of Interleukin-6 in Chronic Obstructive Pulmonary Disease

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posted on 2011-10-11, 00:00 authored by van Durme Y.M.T.A., Lahousse L., Verhamme K.M.C., Stolk L., Eijgelsheim M., Loth D.W., Uitterlinden A.G., Breteler M.M.B., Joos G.F., Hofman A.
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.

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