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Wang Z, Xie Z, Lu Q, et al. Beyond Genetics: What Causes Type 1 Diabetes. Clin Rev Allergy Immunol. 2017;52(2):273-286doi: 10.1007/s12016-016-8592-1.
Wang, Z., Xie, Z., Lu, Q., Chang, C., & Zhou, Z. (2017). Beyond Genetics: What Causes Type 1 Diabetes. Clinical reviews in allergy & immunology, 52(2), 273-286. https://doi.org/10.1007/s12016-016-8592-1
Wang, Zhen, et al. "Beyond Genetics: What Causes Type 1 Diabetes." Clinical reviews in allergy & immunology vol. 52,2 (2017): 273-286. doi: https://doi.org/10.1007/s12016-016-8592-1
Wang Z, Xie Z, Lu Q, Chang C, Zhou Z. Beyond Genetics: What Causes Type 1 Diabetes. Clin Rev Allergy Immunol. 2017 Apr;52(2):273-286. doi: 10.1007/s12016-016-8592-1. PMID: 27878451.
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Clin Rev Allergy Immunol. 2017 Apr;52(2):273-286. doi: 10.1007/s12016-016-8592-1.

Beyond Genetics: What Causes Type 1 Diabetes.

Clinical reviews in allergy & immunology

Zhen Wang, Zhiguo Xie, Qianjin Lu, Christopher Chang, Zhiguang Zhou

Affiliations

  1. Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, 139 Renmin Middle Rd, Changsha, Hunan, 410011, China.
  2. Department of Dermatology, 2nd Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Renmin Middle Rd, Changsha, Hunan, 410011, China.
  3. Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, USA.
  4. Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, 139 Renmin Middle Rd, Changsha, Hunan, 410011, China. [email protected].

PMID: 27878451 DOI: 10.1007/s12016-016-8592-1

Abstract

Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated β cell destruction in the pancreas of genetically susceptible individuals. Extensive familial and population genetic studies uncovered the strong linkage and association between HLA gene variants and T1D. Non-HLA genes have also been associated with T1D, such as INS, CTLA4, and PTPN22. T1D is considered as one of the most heritable common diseases. However, evidence that monozygotic twins have incomplete concordance of disease susceptibility provides convincing proof that environmental factors also play important roles in the pathogenesis of the disease. Environmental factors can induce the alterations of gene expression via epigenetic mechanisms. Epigenetic modifications refer to the alterations in gene expression without changes of the DNA sequence, but instead occur as a result of DNA methylation, histone modifications, and miRNA regulation. Aberrant epigenetic modifications will cause the dysregulation of gene expression, thus leading to a variety of human diseases. There are significant differences in DNA methylation, histone modifications, and miRNA profiling found in T1D patients compared with healthy individuals. Epigenetic modifications contribute to the pathogenesis of T1D mainly by regulating the expression of susceptible genes in T1D. These susceptible genes are involved in antigen presentation (such as HLA), immune tolerance (such as FOXP3 and CTLA4), autoreactive T cell response (such as GAD65), and β cell functions (such as INS). A better understanding of epigenetic mechanisms for regulating susceptible genes of T1D will help identify candidates that target epigenetic pathways to control and/or prevent T1D. Knowledge of epigenetic changes in T1D also provides us with potential biomarkers for diagnosis, prognostication, personalized treatment, and prevention of the disease.

Keywords: DNA methylation; Environmental factors; Epigenetics; Genetics; Histone modifications; Type 1 diabetes; miRNA

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