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Herder, C.* ; Nuotio, M.L.* ; Shah, S.* ; Blankenberg, S.* ; Brunner, E.J.* ; Carstensen, M.* ; Gieger, C. ; Grallert, H. ; Jula, A.* ; Kähönen, M.* ; Kettunen, J.* ; Kivimaki, M.* ; Koenig, W.* ; Kristiansson, K.* ; Langenberg, C.* ; Lehtimäki, T.* ; Luotola, K.* ; Marzi, C. ; Müller, C.* ; Peters, A. ; Prokisch, H. ; Raitakari, O.* ; Rathmann, W.* ; Roden, M.* ; Salmi, M.* ; Schramm, K. ; Swerdlow, D.I.* ; Tabak, A.G.* ; Thorand, B. ; Wareham, N.J.* ; Wild, P.S.* ; Zeller, T.* ; Hingorani, A.D.* ; Witte, D.R.* ; Kumari, M.* ; Perola, M.* ; Salomaa, V.*

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

Diabetes 63, 4343-4359 (2014)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The pro-inflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and beta-cell dysfunction, whereas higher circulating IL-1 receptor antagonist (IL-1RA - an endogenous inhibitor of IL-1β - has been suggested to improve glycemia and beta-cell function in patients with type 2 diabetes. In order 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 7 discovery and 4 replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL-1RN locus, n=13,955, P=2.76x10(-21); and rs6759676, closest gene locus IL1F10, n=13,994, P=1.73x10(-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 and lower homeostasis model assessment insulin resistance (HOMA-IR). In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL-1RN and IL-1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 63, Heft: 12, Seiten: 4343-4359 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Begutachtungsstatus Peer reviewed