Association of Variation in the Interleukin-1 Gene Family with Diabetes and Glucose Homeostasis. Export

@article{citeulike:5938589, abstract = {Objective: Proinflammatory cytokine IL-1beta is capable of decreasing insulin-induced glucose transport. Therefore, we hypothesized that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and diabetes. Design and Outcome Measures: Fifteen haplotype-tagging single-nucleotide polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes were determined in a Finnish population survey (n = 6771). Glucose and insulin concentrations were measured, and indices of insulin resistance and beta-cell function were calculated using the homeostasis model assessment. Two-hour oral glucose tolerance tests were carried out on a subsample of 1390 participants. Associations with prevalent diabetes were tested for replication in a sample of European myocardial infarction survivors (n = 972). Results: The minor allele of the IL-1beta rs1143634(G-->A) was associated with higher blood glucose than the major allele: 5.37, 5.41, and 5.48 mmol/liter for the GG, AG, and AA genotypes, respectively (multivariate adjusted P for trend <0.0001; Bonferroni corrected P = 0.00096). The 2-h glucose was also higher (6.45 and 7.20 mmol/liter for the GG vs. AA; P = 0.003, Bonferroni corrected P = 0.045). The haplotype ACG of rs1143634, rs3917356, and rs16944 associated with higher glucose, higher homeostasis model assessment for insulin resistance index, higher 2-h insulin, and prevalent diabetes (adjusted rate ratio = 1.54; 95\% confidence interval = 1.03-2.30; P = 0.037). The association with prevalent diabetes was replicated among European myocardial infarction survivors (rate ratio = 2.09; 95\% confidence interval = 1.17-3.76; P = 0.013). Conclusions: These results suggest that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and prevalent diabetes.}, author = {Luotola, Kari and P\"{a}\"{a}kk\"{o}nen, Rauni and Alanne, Mervi and Lanki, Timo and Moilanen, Leena and Surakka, Ida and Pietil\"{a}, Arto and K\"{a}h\"{o}nen, Mika and Nieminen, Markku S. and Kes\"{a}niemi, Y. Antero and Peters, Annette and Jula, Antti and Perola, Markus and Salomaa, Veikko and {for the Health 2000 and AIRGENE Study Groups}}, citeulike-article-id = {5938589}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/jc.2009-0666}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19820020}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19820020}, day = {9}, doi = {10.1210/jc.2009-0666}, issn = {1945-7197}, journal = {The Journal of clinical endocrinology and metabolism}, keywords = {genetic-polymorphism, il-1}, month = {October}, posted-at = {2009-11-04 22:41:35}, priority = {2}, title = {Association of Variation in the Interleukin-1 Gene Family with Diabetes and Glucose Homeostasis.}, url = {http://dx.doi.org/10.1210/jc.2009-0666}, year = {2009} }

TY - JOUR ID - citeulike:5938589 L3 - citeulike-article-id:5938589 N2 - Objective: Proinflammatory cytokine IL-1beta is capable of decreasing insulin-induced glucose transport. Therefore, we hypothesized that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and diabetes. Design and Outcome Measures: Fifteen haplotype-tagging single-nucleotide polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes were determined in a Finnish population survey (n = 6771). Glucose and insulin concentrations were measured, and indices of insulin resistance and beta-cell function were calculated using the homeostasis model assessment. Two-hour oral glucose tolerance tests were carried out on a subsample of 1390 participants. Associations with prevalent diabetes were tested for replication in a sample of European myocardial infarction survivors (n = 972). Results: The minor allele of the IL-1beta rs1143634(G-->A) was associated with higher blood glucose than the major allele: 5.37, 5.41, and 5.48 mmol/liter for the GG, AG, and AA genotypes, respectively (multivariate adjusted P for trend <0.0001; Bonferroni corrected P = 0.00096). The 2-h glucose was also higher (6.45 and 7.20 mmol/liter for the GG vs. AA; P = 0.003, Bonferroni corrected P = 0.045). The haplotype ACG of rs1143634, rs3917356, and rs16944 associated with higher glucose, higher homeostasis model assessment for insulin resistance index, higher 2-h insulin, and prevalent diabetes (adjusted rate ratio = 1.54; 95% confidence interval = 1.03-2.30; P = 0.037). The association with prevalent diabetes was replicated among European myocardial infarction survivors (rate ratio = 2.09; 95% confidence interval = 1.17-3.76; P = 0.013). Conclusions: These results suggest that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and prevalent diabetes. JF - The Journal of clinical endocrinology and metabolism SN - 1945-7197 TI - Association of Variation in the Interleukin-1 Gene Family with Diabetes and Glucose Homeostasis. KW - genetic-polymorphism KW - il-1 AU - Luotola, Kari AU - Pääkkönen, Rauni AU - Alanne, Mervi AU - Lanki, Timo AU - Moilanen, Leena AU - Surakka, Ida AU - Pietilä, Arto AU - Kähönen, Mika AU - Nieminen, Markku AU - Kesäniemi, Antero AU - Peters, Annette AU - Jula, Antti AU - Perola, Markus AU - Salomaa, Veikko PY - 2009/10/09/ UR - http://dx.doi.org/10.1210/jc.2009-0666 ER -