Genetic Aspects of type 1 diabetes

Abstract

Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic beta-cells in genetically predisposed individuals, eventually resulting in severe insulin deficiency. It is the most common form of diabetes in children and adolescents. Genetic susceptibility plays a crucial role in development of T1DM. The human leukocyte antigen complex plays a key role in the pathogenesis of T1DM. Furthermore, genome-wide association studies and linkage analysis have recently made a significant contribution to current knowledge relative to the impact of genetics on T1DM development and progression. This review focuses on current knowledge of genetics as a pathogenesis for T1DM. It also discusses mechanisms by which genes influence the risk of developing T1DM as well as the clinical and research applications of genetic risk scores in T1DM.

Genetic Ancestry Inferred From Autosomal and Y Chromosome Markers and HLA Genotypes in Type 1 Diabetes From an Admixed Brazilian Population.

“…In a large analysis of the T1D population in all Brazilian regions, a result similar to ours was found 46 . It is reported that approximately 30% of individuals with T1D have DR3/DR4 in heterozygosity 6,47 , corroborating our ndings.…”

“…Certain combinations of alleles are found in speci c haplotypes of the HLA-DRB1~DQA1~DQB1 genes, varying between some ethnic groups, conferring susceptibility or protection to the disease 3,4,5 . In Europeans, the greatest risk to the disease is associated with the haplotypes DRB1*04:01/02/04/05~DQA1*03~DQB1*03:02 and DRB1* 03:01~DQA1* 05:01~DQB1* 02:01 1,6,7 . In patients of African origin, additional haplotypes are associated with risk, such as DRB1 * 09: 01~DQA1* 03:01~DQB1* 02:01 and DRB1* 07:01~DQA1* 03:01~DQB1* 02:01 8 .…”

A non‐codingRNASEH1gene variant associates with type 1 diabetes and interacts withHLA tagSNPsin families from Colombia

“…On the other hand, of the 45 tagSNPs focused on inferring classic HLA alleles, 14 showed statistically significant association (Table 4). The association was more significant for the tagSNPs of the class II alleles than for the class I alleles, which is consistent with the literature 30‐32 . SNP rs2187668 (tagSNP for haplotype DQ2.5) and rs7454108 (tagSNPs for haplotype DQ8) have been found associated with susceptibility to T1D and also with other autoimmune diseases 33 in various populations worldwide 34,35 .…”

“…The association was more significant for the tagSNPs of the class II alleles than for the class I alleles, which is consistent with the literature. [30][31][32] SNP rs2187668 (tagSNP for haplotype DQ2.5) and…”

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

“…In fact, the variation of the DNA methylation within the INS gene is suspected to regulate INS gene transcription in the pancreatic β-cells as well as the medullary thymic epithelial cells. These two tissues are known to be the sites where INS gene is expressed and to be the center of the mechanisms of T1D (43). One study highlighted the relationship between the immune response the DNA methylation changes at Ins1 and Ins2 genes that occurs in both β-cells of non-obese diabetic mice and human β-cells (41).…”