UZH-Logo

Maintenance Infos

A common functional variant on the pro-inflammatory Interleukin-6 gene may modify the association between long-term PM10 exposure and diabetes


Eze, Ikenna C; Imboden, Medea; Kumar, Ashish; Adam, Martin; von Eckardstein, Arnold; Stolz, Daiana; Gerbase, Margaret W; Künzli, Nino; Turk, Alexander; Schindler, Christian; Kronenberg, Florian; Probst-Hensch, Nicole (2016). A common functional variant on the pro-inflammatory Interleukin-6 gene may modify the association between long-term PM10 exposure and diabetes. Environmental Health, 15:39.

Abstract

BACKGROUND Air pollutants have been linked to type 2 diabetes (T2D), hypothesized to act through inflammatory pathways and may induce interleukin-6 gene (IL6) in the airway epithelium. The cytokine interleukin-6 may impact on glucose homeostasis. Recent meta-analyses showed the common polymorphisms, IL6 -572G > C and IL6 -174G > C to be associated with T2D risk. These IL6 variants also influence circulatory interleukin-6 levels. We hypothesize that these common functional variants may modify the association between air pollutants and T2D. METHODS We cross-sectionally studied 4410 first follow-up participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases (SAPALDIA), aged 29 to 73 years who had complete data on genotypes, diabetes status and covariates. We defined diabetes as self-reported physician-diagnosed, or use of diabetes medication or non-fasting glucose >11.1 mmol/L or HbA1c > 0.065. Air pollution exposure was 10-year mean particulate matter <10 μm in diameter (PM10) assigned to participants' residences using a combination of dispersion modelling, annual trends at monitoring stations and residential history. We derived interaction terms between PM10 and genotypes, and applied mixed logistic models to explore genetic interactions by IL6 polymorphisms on the odds of diabetes. RESULTS There were 252 diabetes cases. Respective minor allele frequencies of IL6 -572G > C and IL6 -174G > C were 7 and 39 %. Mean exposure to PM10 was 22 μg/m(3). Both variants were not associated with diabetes in our study. We observed a significant positive association between PM10 and diabetes among homozygous carriers of the pro-inflammatory major G-allele of IL6 -572G > C [Odds ratio: 1.53; 95 % confidence interval (1.22, 1.92); P interaction (additive) = 0.003 and P interaction (recessive) = 0.006]. Carriers of the major G-allele of IL6 -174G > C also had significantly increased odds of diabetes, but interactions were statistically non-significant. CONCLUSIONS Our results on the interaction of PM10 with functionally well described polymorphisms in an important pro-inflammatory candidate gene are consistent with the hypothesis that air pollutants impact on T2D through inflammatory pathways. Our findings, if confirmed, are of high public health relevance considering the ubiquity of the major G allele, which puts a substantial proportion of the population at risk for the development of diabetes as a result of long-term exposure to air pollution.

Abstract

BACKGROUND Air pollutants have been linked to type 2 diabetes (T2D), hypothesized to act through inflammatory pathways and may induce interleukin-6 gene (IL6) in the airway epithelium. The cytokine interleukin-6 may impact on glucose homeostasis. Recent meta-analyses showed the common polymorphisms, IL6 -572G > C and IL6 -174G > C to be associated with T2D risk. These IL6 variants also influence circulatory interleukin-6 levels. We hypothesize that these common functional variants may modify the association between air pollutants and T2D. METHODS We cross-sectionally studied 4410 first follow-up participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases (SAPALDIA), aged 29 to 73 years who had complete data on genotypes, diabetes status and covariates. We defined diabetes as self-reported physician-diagnosed, or use of diabetes medication or non-fasting glucose >11.1 mmol/L or HbA1c > 0.065. Air pollution exposure was 10-year mean particulate matter <10 μm in diameter (PM10) assigned to participants' residences using a combination of dispersion modelling, annual trends at monitoring stations and residential history. We derived interaction terms between PM10 and genotypes, and applied mixed logistic models to explore genetic interactions by IL6 polymorphisms on the odds of diabetes. RESULTS There were 252 diabetes cases. Respective minor allele frequencies of IL6 -572G > C and IL6 -174G > C were 7 and 39 %. Mean exposure to PM10 was 22 μg/m(3). Both variants were not associated with diabetes in our study. We observed a significant positive association between PM10 and diabetes among homozygous carriers of the pro-inflammatory major G-allele of IL6 -572G > C [Odds ratio: 1.53; 95 % confidence interval (1.22, 1.92); P interaction (additive) = 0.003 and P interaction (recessive) = 0.006]. Carriers of the major G-allele of IL6 -174G > C also had significantly increased odds of diabetes, but interactions were statistically non-significant. CONCLUSIONS Our results on the interaction of PM10 with functionally well described polymorphisms in an important pro-inflammatory candidate gene are consistent with the hypothesis that air pollutants impact on T2D through inflammatory pathways. Our findings, if confirmed, are of high public health relevance considering the ubiquity of the major G allele, which puts a substantial proportion of the population at risk for the development of diabetes as a result of long-term exposure to air pollution.

Citations

2 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

4 downloads since deposited on 05 Jul 2016
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Language:English
Date:2016
Deposited On:05 Jul 2016 14:21
Last Modified:08 Sep 2016 07:26
Publisher:BioMed Central
ISSN:1476-069X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12940-016-0120-5
PubMed ID:26911440

Download

[img]
Preview
Content: Published Version
Filetype: PDF
Size: 841kB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations