Molecular Genetics of Type 1 Diabetes

Abstract

Approximately one third of susceptibility to type 1 diabetes is determined by genetic factors. These factors are termed susceptibility genes as they modify the risk of diabetes but are neither necessary nor sufficient for disease to develop. More than 20 different regions in the human genome have been suggested to contain diabetes susceptibility genes. The IDDM1 locus, which encompasses the human leukocyte antigen (HLA) gene complex on chromosome 6p, is the major genetic risk factor, accounting for approximately 40% of inherited susceptibility. The HLA‐DQ genes within this region are thought to be primary risk determinants of IDDM1 , although other genes also contribute. The IDDM2 locus, which maps to a variable number of tandem repeats region close to the insulin gene on chromosome 11p, contributes approximately 10% of genetic predisposition. The precise location and identity of other diabetes susceptibility genes remain unknown. These loci, however, are likely to make much smaller contributions to disease risk. Further research is necessary to identify all the genetic susceptibility factors for type 1 diabetes and to determine how they interact, with each other and with environmental factors, to influence disease risk.

Association of Cytotoxic T-Lymphocyte Antigen-4 Gene Polymorphism with Type 1 Diabetes Mellitus: In silico Analysis of Biological Features of CTLA-4 Protein on Ethiopian Population

“…5,6 Type 2 Diabetes Mellitus (T2DM) is caused by both decreased insulin secretion and resistance to its action, which is frequently caused by obese relative insufficiency. [7][8][9][10] Diabetes mellitus is a group of diseases with a complicated etiology involving the interaction of environmental exposures and an individual's genetic make-up. 11 There is a substantial gap in understanding the burden on a national and international level due to the accuracy and sufficiency of data for monitoring DM patients, especially in developing countries.…”

Expressão, localização e modulação de NADPH oxidases por citocinas pró-inflamatórias na célula β pancreática.

“…O DM1 é poligênico: mais de 50 loci conferindo risco de desenvolver DM1 são conhecidos e muitos destes tem função imunológica (ATKINSON et al, 2020;KELLY et al, 2015). O risco de DM1 é 0,3% na população geral.…”

“…Variações dos genes do antígeno leucocitário humano (HLA) no cromossomo 6p21.31 explicam 40-50% da hereditariedade do DM1 (KELLY et al, 2015). Estes genes codificam o complexo principal de histocompatibilidade (MHC) de classe I e II, responsáveis pela apresentação de antígenos aos linfócitos T. Os genes HLA-DQ e HLA-DR conferem o maior risco de DM1.…”

“…Estes genes codificam o complexo principal de histocompatibilidade (MHC) de classe I e II, responsáveis pela apresentação de antígenos aos linfócitos T. Os genes HLA-DQ e HLA-DR conferem o maior risco de DM1. O gene insulina confere o segundo maior risco (KELLY et al, 2015). Assim como HLA, outros genes importantes de risco ao DM1 (CTLA4, PTPN22, IL2RA, IHIF1) também tem função imunológica (KELLY et al, 2015;PUGLIESE, 2015).…”

“…O gene insulina confere o segundo maior risco (KELLY et al, 2015). Assim como HLA, outros genes importantes de risco ao DM1 (CTLA4, PTPN22, IL2RA, IHIF1) também tem função imunológica (KELLY et al, 2015;PUGLIESE, 2015).…”