1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

Objective: Proinflammatory cytokine IL-1β 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-1α, IL-1β, 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 β-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-1β 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, respectiv...

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

Comorbid states of diseases significantly complicate diagnosis and treatment. Molecular mechanisms of comorbid states of asthma and hypertension are still poorly understood. Prioritization is a way for identifying genes involved in complex phenotypic traits. Existing methods of prioritization consider genetic, expression and evolutionary data, molecular-genetic networks and other. In the case of molecular-genetic networks, as a rule, protein-protein interactions and KEGG networks are used. ANDSystem allows reconstructing associative gene networks, which include more than 20 types of interactions, including protein-protein interactions, expression regulation, transport, catalysis, etc. In this work, a set of genes has been prioritized to find genes potentially involved in asthma and hypertension comorbidity. The prioritization was carried out using well-known methods (ToppGene and Endeavor) and a cross-talk centrality criterion, calculated by analysis of associative gene networks from ANDSystem. The identified genes, including IL1A, CD40LG, STAT3, IL15, FAS, APP, TLR2, C3, IL13 and CXCL10, may be involved in the molecular mechanisms of comorbid asthma/hypertension. An analysis of the dynamics of the frequency of mentioning the most priority genes in scientific publications revealed that the top 100 priority genes are significantly enriched with genes with increased positive dynamics, which may be a positive sign for further studies of these genes.

/pdf/search-for-new-candidate-genes-involved-in-the-comorbidity-riiiwpy0mu.pdf

Search for New Candidate Genes Involved in the Comorbidity of Asthma and Hypertension Based on Automatic Analysis of Scientific Literature.

Ankylosing spondylitis (AS) is a common and highly heritable inflammatory arthropathy. Although the gene HLA-B27 is almost essential for the inheritance of the condition, it alone is not sufficient to explain the pattern of familial recurrence of the disease. We have previously demonstrated suggestive linkage of AS to chromosome 2q13, a region containing the interleukin 1 (IL-1) family gene cluster, which includes several strong candidates for involvement in the disease. In the current study, we describe strong association and transmission of IL-1 family gene cluster single-nucleotide polymorphisms and haplotypes with AS.

The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis

Abstract.  Luotola K, Pietilä A, Zeller T, Moilanen L, Kähönen M, Nieminen MS, Kesäniemi YA, Blankenberg S, Jula A, Perola M, Salomaa V (Helsinki University Hospital, Helsinki; National Institute for Health and Welfare, Helsinki, Finland; University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany; University Hospital of Kuopio, Kuopio; Tampere University Hospital and Medical School, University of Tampere, Tampere; University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu; National Institute for Health and Welfare, Turku; and Institute for Molecular Medicine Finland, Helsinki, Finland). Associations between interleukin‐1 (IL‐1) gene variations or IL‐1 receptor antagonist levels and the development of type 2 diabetes. J Intern Med 2010; 269: 322–332.

Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes

The interleukin-1α (IL-1α) gene appears to play a role in the pathogenesis of type 1 diabetes (T1D). Therefore, the aim of this study was to investigate the contribution of the IL-1 rs1800587 gene polymorphism to susceptibility to T1D in Chinese children. This case-control study included 332 Chinese children with T1D and 332 healthy controls. Identification of genetic variants of rs1800587 in the IL-1α gene was performed by polymerase chain reaction amplification. The IL-1α rs1800587 polymorphism demonstrated a significant association with T1D risk. The allelic frequency significantly differed between the T1D and control groups [odds ratio (OR) = 0.7; 95% confidence interval (CI) = 0.52-0.86; P = 0.002]. Furthermore, significant differences were observed in the dominant model (CC/CT + TT; OR = 0.6; 95%CI = 0.46-0.85; P = 0.003). In T1D patients, the prevalence of hypertension in T allele carriers was 4.2-fold higher than that in C allele carriers, (95%CI = 2.67-6.58; P < 0.001). In conclusion, the present study found evidence of a significant association between the rs1800587 polymorphism in the IL-1α gene and T1D.

/pdf/association-of-il-1a-gene-polymorphism-with-susceptibility-rq3ga2dddt.pdf

Association of IL-1α gene polymorphism with susceptibility to type 1 diabetes in Chinese children.

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Association of IL-1α gene polymorphism with susceptibility to type 1 diabetes in Chinese children.