Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes
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Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes. / Luotola, K; Pietilä, A; Zeller, T; Moilanen, L; Kähönen, M; Nieminen, M S; Kesäniemi, Y A; Blankenberg, S; Jula, A; Perola, M; Salomaa, V; Health 2000 and FINRISK97 Studies.
In: J INTERN MED, Vol. 269, No. 3, 03.2011, p. 322-332.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes
AU - Luotola, K
AU - Pietilä, A
AU - Zeller, T
AU - Moilanen, L
AU - Kähönen, M
AU - Nieminen, M S
AU - Kesäniemi, Y A
AU - Blankenberg, S
AU - Jula, A
AU - Perola, M
AU - Salomaa, V
AU - Health 2000 and FINRISK97 Studies
N1 - © 2010 The Association for the Publication of the Journal of Internal Medicine.
PY - 2011/3
Y1 - 2011/3
N2 - OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes.DESIGN: Two observational prospective cohort studies.SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively.SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997.RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes.CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.
AB - OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes.DESIGN: Two observational prospective cohort studies.SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively.SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997.RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes.CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.
KW - Adult
KW - Aged
KW - Biomarkers/blood
KW - C-Reactive Protein/analysis
KW - Cohort Studies
KW - Diabetes Mellitus, Type 2/blood
KW - Female
KW - Follow-Up Studies
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Humans
KW - Interleukin 1 Receptor Antagonist Protein/blood
KW - Interleukin-1/genetics
KW - Male
KW - Metabolic Syndrome/blood
KW - Middle Aged
KW - Sex Factors
U2 - 10.1111/j.1365-2796.2010.02294.x
DO - 10.1111/j.1365-2796.2010.02294.x
M3 - SCORING: Journal article
C2 - 21205020
VL - 269
SP - 322
EP - 332
JO - J INTERN MED
JF - J INTERN MED
SN - 0954-6820
IS - 3
ER -
