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.
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 COPDpatients. 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.
Authors: Eric Bradford; Sean Jacobson; Jason Varasteh; Alejandro P Comellas; Prescott Woodruff; Wanda O'Neal; Dawn L DeMeo; Xingnan Li; Victor Kim; Michael Cho; Peter J Castaldi; Craig Hersh; Edwin K Silverman; James D Crapo; Katerina Kechris; Russell P Bowler Journal: Respir Res Date: 2017-10-24
Authors: E C Oelsner; T D Pottinger; K M Burkart; M Allison; S G Buxbaum; N N Hansel; R Kumar; E K Larkin; L A Lange; L R Loehr; S J London; G T O'Connor; G Papanicolaou; M F Petrini; D Rabinowitz; S Raghavan; S Redline; B Thyagarajan; R P Tracy; J B Wilk; W B White; S S Rich; R G Barr Journal: Biomarkers Date: 2013-04-05 Impact factor: 2.658