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Type 1 diabetes: genes associated with disease development.

ABSTRACT: Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030. In 2015 American Diabetes Association (ADA) announced that 30.3 million Americans (that is 9.4% of the overall population) had diabetes of which only approximately 1.25 million had T1D. Nowadays, T1D represents roughly 10% of adult diabetes cases total. Multiple genetic abnormalities at different loci have been found to contribute to type 1 diabetes development. The analysis of genome-wide association studies (GWAS) of T1D has identified over 50 susceptible regions (and genes within these regions). Many of these regions are defined by single nucleotide polymorphisms (SNPs) but molecular mechanisms through which they increase or lower the risk of diabetes remain unknown. Genetic factors (in existence since birth) can be detected long before the emergence of immunological or clinical markers. Therefore, a comprehensive understanding of the multiple genetic factors underlying T1D is extremely important for further clinical trials and development of personalized medicine for diabetic patients. We present an overview of current studies and information about regions in the human genome associated with T1D. Moreover, we also put forward information about epigenetic modifications, non-coding RNAs and environmental factors involved in T1D development and onset.

SUBMITTER: Klak M

PROVIDER: S-EPMC7882399 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Type 1 diabetes: genes associated with disease development.

Klak Marta M Gomółka Magdalena M Kowalska Patrycja P Cichoń Justyna J Ambrożkiewicz Filip F Serwańska-Świętek Marta M Berman Andrzej A Wszoła Michał M

Central-European journal of immunology 20200101 4

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030. In 2015 American Diabetes Association (ADA) announced that 30.3 million Americans (that is 9.4% of the overall population) had ...[more]

PMID: 33658892

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Project description:Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip. Cox proportional hazards analyses were performed to discover the SNPs associated with the risk for IA, T1D, or both. Three regions were associated with the risk of developing any persistent confirmed islet autoantibody: one known region near SH2B3 (HR = 1.35, p = 3.58 × 10-7) with Bonferroni-corrected significance and another known region near PTPN22 (HR = 1.46, p = 2.17 × 10-6) and one novel region near PPIL2 (HR = 2.47, p = 9.64 × 10-7) with suggestive evidence (p < 10-5). Two known regions (PTPN22: p = 2.25 × 10-6, INS; p = 1.32 × 10-7) and one novel region (PXK/PDHB: p = 8.99 × 10-6) were associated with the risk for multiple islet autoantibodies. First appearing islet autoantibodies differ with respect to association. Two regions (INS: p = 5.67 × 10-6 and TTC34/PRDM16: 6.45 × 10-6) were associated if the fist appearing autoantibody was IAA and one region (RBFOX1: p = 8.02 × 10-6) was associated if the first appearing autoantibody was GADA. The analysis of T1D identified one region already known to be associated with T1D (INS: p = 3.13 × 10-7) and three novel regions (RNASET2, PLEKHA1, and PPIL2; 5.42 × 10-6 > p > 2.31 × 10-6). These results suggest that a number of low frequency variants influence the risk of developing IA and/or T1D and these variants can be identified by large prospective cohort studies using a survival analysis approach.

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Type 1 diabetes: genes associated with disease development.

Publications

Type 1 diabetes: genes associated with disease development.

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