Genetic factors type 1 diabetes mellitus

Currently it is well known the requirement of a predispositionspecific gene for the development of DM1. However,genetic correlation evidenced in twins is not complete, sincecorresponds to only 50% in monozygotic twins and is less than 10%in dizygotic. Still, in the long term follow, mostidentical twins with DM1 eventually express autoantibodiesanti-islet and progress to diabetes, although these mayappear until 30 years after the first twin developsdiabetes, which implies that the sensitivity persists for life (27).Multiple genetic polymorphisms are involved in the risk ofDM1, resulting from large genetic association studies, includingCoeliac disease-related loci, but most of thesegenes have small effects and multiple variants that do not allowuse as predictors of risk (27). Rarely should DM1defects by mutation of a single gene. When the form is submittedmonogenic usually accompanied by other autoimmune conditionsaltered regulatory pathways. Examples include syndromeIPEX (immune dysregulation, polyendocrinopathy, enteropathy linkedto X) by Foxp3 gene mutation or autoimmune polyendocrine syndrometype 1 (APS-1) by altering the air transcription factorsevere autoimmune conditions leads to inhibition of expression byperipheral molecules (27). It should highlight the role of CCR5 association,by an insertion of 32 base pairs at a chemokine receptor,with loss of function thereof, and in the case of homozygous,a decrease of 2 times the risk of DM1 (27-29). The main genesrisk involved in the complex are those corresponding to the higher ofcompatibility (MHC) and HLA. The region of chromosome 6p21 (calledlocus IDDM1 insulin dependent diabetes mellitus) is critical todevelopment of many autoimmune diseases, and has been determinedtheir single nucleotide polymorphisms increase somodest risk (OR 1.2 to 1.3) (27,28,30). However, this tendency strengthensthe concept that HLA class II molecules are keysusceptibility, including haplotype DRB1 * 1501-DQA1 * 0102 -DQB1 * 0602, found in over 20% of the population, but only in 1% of patients dominant confers protection againstDM1 (27). In the final spectrum are individuals susceptibilityDR3/4-DQ8 with heterozygous haplotype with increased risk.However, only 30-50% of patients presenting, reflectinggenetic complexity at the DM1 engagement (27,28) (Table 1). The ofInsulin is one of the major genes involved in the developmentof DM1. Located on chromosome 11, its mutations favorRecognition of insulin as an autoantigen and contribute tosusceptibility, since the polymorphism in the promoter region of the gene.Such tandem repeats zone presents variable number (VNTRs)conferring increased risk in the case of VNTR type 1 (repetitionshort) or protective effect in type 3 (long repeats) (27). The genePTPN22, recently identified, encodes a protein tyrosine phosphataselymphoid (LYP), whose allelic variants confer risk in otherautoimmune diseases, acting as part of the signal axis,crucial for the activation of autoreactive T cells in the periphery.Similarly, the CTLA-4 is an allele encoding associated protein 4Cytotoxic T lymphocytes, which is essential for proper regulationnegative immune responses, and mutations have also beenother entities involved in autoimmune lupus erythematosus andrheumatoid arthritis (27,28). Finally, it is estimated that 48% aggregationfamily can claim to known loci, and contributes CMHwith 41%. For example, the brothers with the highest risk HLA DR and DQ(DR3/DR4 heterozygotes) that inherit both HLA identical regionsmay be at risk of developing autoimmunity as high as80%, with a similar risk of diabetes, the lifetime risk isincreases sharply for relatives of individuals with DM1,an average of 6% for their offspring, 5% for siblings and 50%in identical twins (dizygotic if the risk is similar to brothersno twins), compared to 0.4% in patients with no family history90% in first-degree relatives with two types of autoantibodiespositive markers