COPD Risk and IL6 Gene Single Nucleotide Polymorphisms

COPD, x ray
COPD, x ray
What is the relationship COPD risk and genetic alterations of the IL6 gene across genotypes? An analysis of 18 studies addresses this question.

A chronic obstructive pulmonary disease (COPD)-susceptibility locus may be the interleukin 6 (IL6) gene rs1818879, according to results of a literature review-based analysis published recently in Gene. Taking into account all genetic inheritance models, the mutation of the IL6 gene is associated with a lower risk for COPD.

The IL6 gene has been linked to COPD in previous studies, suggesting that IL6 genetic alterations may be associated with COPD risk. However, explanation of genetic heritability of COPD by known genetic alterations remains unclear. Researchers sought to investigate the connection of 3 variant forms of DNA sequence in the IL6 gene with COPD.

To accomplish this, the investigators conducted a review and analysis of 18 studies from 2005 to 2021 that included 4815 participants. All studies included had a case-control design, had COPD as a clinical endpoint, and included genotype and allele accounts of any single nucleotide polymorphisms in the IL6 gene between patients with COPD and a control group.

Analysis revealed no significant association between COPD and rs1800795 or rs1800797. However, there was a statistical significance across 4 genetic modes of inheritance for rs1818879 (P <.05). Study heterogeneity led to subgroup analysis according to COPD diagnosis (defined by the Global Initiative for Chronic Obstructive Lung Disease [GOLD] or European Respiratory Society [ERS] guidelines), matched condition, and race (White, Asian, or other).

Researchers concluded that “the mutation of rs1818879 was associated with a reduced risk for COPD under all genetic models of inheritance.” They also stated that their subgroup analysis of COPD diagnosis, matched condition, and race showed these factors to be the likely cause of “between-study heterogeneity.” They added, “whether rs1818879 is a COPD-susceptibility locus requires further independent validations.”

Study limitations included: the cross-sectional design of the case-control studies utilized for analysis, which prevented causality inferences; selection bias, as only articles in English were used in this analysis; the use of only 3 single nucleotide polymorphisms in the analysis; and lack of consideration of gene-gene and gene-environment interactions.


Hao Y, Zhou Q, Sun Y, Niu W, Du J. Association of three single nucleotide polymorphisms in interleukin 6 gene with risk of chronic obstructive pulmonary disease. Gene. Published online April 12, 2022. doi:10.1016/j.gene.2022.146467