Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits
Standard
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; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, 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.
in: DIABETES, Jahrgang 63, Nr. 12, 12.2014, S. 4343-4359.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits
AU - Herder, Christian
AU - Nuotio, Marja-Liisa
AU - Shah, Sonia
AU - Blankenberg, Stefan
AU - Brunner, Eric J
AU - Carstensen, Maren
AU - Gieger, Christian
AU - Grallert, Harald
AU - Jula, Antti
AU - Kähönen, Mika
AU - Kettunen, Johannes
AU - Kivimäki, Mika
AU - Koenig, Wolfgang
AU - Kristiansson, Kati
AU - Langenberg, Claudia
AU - Lehtimäki, Terho
AU - Luotola, Kari
AU - Marzi, Carola
AU - Müller, Christian
AU - Peters, Annette
AU - Prokisch, Holger
AU - Raitakari, Olli
AU - Rathmann, Wolfgang
AU - Roden, Michael
AU - Salmi, Marko
AU - Schramm, Katharina
AU - Swerdlow, Daniel
AU - Tabak, Adam G
AU - Thorand, Barbara
AU - Wareham, Nick
AU - Wild, Philipp S
AU - Zeller, Tanja
AU - Hingorani, Aroon D
AU - Witte, Daniel R
AU - Kumari, Meena
AU - Perola, Markus
AU - Salomaa, Veikko
N1 - © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - C-Reactive Protein/metabolism
KW - Cohort Studies
KW - Diabetes Mellitus, Type 2/genetics
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Insulin Resistance/genetics
KW - Interleukin 1 Receptor Antagonist Protein/genetics
KW - Interleukin-1/genetics
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Protective Factors
KW - Young Adult
U2 - 10.2337/db14-0731
DO - 10.2337/db14-0731
M3 - SCORING: Journal article
C2 - 24969107
VL - 63
SP - 4343
EP - 4359
JO - DIABETES
JF - DIABETES
SN - 0012-1797
IS - 12
ER -
