Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits

Herder, Christian, Nuotio, Marja-Liisa, Shah, Sonia, Blankenberg, Stefan, Brunner, Eric J., Carstensen, Maren, Gieger, Christian, Grallert, Harald, Jula, Antti, Kahonen, Mika, Kettunen, Johannes, Kivimaki, Mika, Koenig, Wolfgang, Kristiansson, Kati, Langenberg, Claudia, Lehtimaki, Terho, Luotola, Kari, Marzi, Carola, Mueller, Christian, Peters, Annette, Prokisch, Holger, Raitakari, Olli, Rathmann, Wolfgang, Roden, Michael, Salmi, Marko, Schramm, Katharina, Swerdlow, Daniel, Tabak, Adam G., Thorand, Barbara, Wareham, Nick, Wild, Philipp S., Zeller, Tanja, Hingorani, Aroon D., Witte, Daniel R., Kumari, Meena, Perola, Markus and Salomaa, Veikko (2014) Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits. Diabetes, 63 12: 4343-4359. doi:10.2337/db14-0731


Author Herder, Christian
Nuotio, Marja-Liisa
Shah, Sonia
Blankenberg, Stefan
Brunner, Eric J.
Carstensen, Maren
Gieger, Christian
Grallert, Harald
Jula, Antti
Kahonen, Mika
Kettunen, Johannes
Kivimaki, Mika
Koenig, Wolfgang
Kristiansson, Kati
Langenberg, Claudia
Lehtimaki, Terho
Luotola, Kari
Marzi, Carola
Mueller, Christian
Peters, Annette
Prokisch, Holger
Raitakari, Olli
Rathmann, Wolfgang
Roden, Michael
Salmi, Marko
Schramm, Katharina
Swerdlow, Daniel
Tabak, Adam G.
Thorand, Barbara
Wareham, Nick
Wild, Philipp S.
Zeller, Tanja
Hingorani, Aroon D.
Witte, Daniel R.
Kumari, Meena
Perola, Markus
Salomaa, Veikko
Title Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits
Journal name Diabetes   Check publisher's open access policy
ISSN 1939-327X
0012-1797
Publication date 2014-12-01
Year available 2014
Sub-type Article (original research)
DOI 10.2337/db14-0731
Open Access Status
Volume 63
Issue 12
Start page 4343
End page 4359
Total pages 17
Place of publication Alexandria VA, United States
Publisher American Diabetes Association
Collection year 2015
Language eng
Formatted abstract
The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10−21] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10−17]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA–raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA–raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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