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Genetic Factors In Type 1 Diabetes

Type 1 Diabetes Risk Factors

Type 1 Diabetes Risk Factors

There are several risk factors that may make it more likely that you’ll develop type 1 diabetes—if you have the genetic marker that makes you susceptible to diabetes. That genetic marker is located on chromosome 6, and it’s an HLA (human leukocyte antigen) complex. Several HLA complexes have been connected to type 1 diabetes, and if you have one or more of those, you may develop type 1. (However, having the necessary HLA complex is not a guarantee that you will develop diabetes; in fact, less than 10% of people with the “right” complex(es) actually develop type 1.) Other risk factors for type 1 diabetes include: Viral infections: Researchers have found that certain viruses may trigger the development of type 1 diabetes by causing the immune system to turn against the body—instead of helping it fight infection and sickness. Viruses that are believed to trigger type 1 include: German measles, coxsackie, and mumps. Race/ethnicity: Certain ethnicities have a higher rate of type 1 diabetes. In the United States, Caucasians seem to be more susceptible to type 1 than African-Americans and Hispanic-Americans. Chinese people have a lower risk of developing type 1, as do people in South America. Geography: It seems that people who live in northern climates are at a higher risk for developing type 1 diabetes. It’s been suggested that people who live in northern countries are indoors more (especially in the winter), and that means that they’re in closer proximity to each other—potentially leading to more viral infections. Conversely, people who live in southern climates—such as South America—are less likely to develop type 1. And along the same lines, researchers have noticed that more cases are diagnosed in the winter in northern countries; the diagnosis rate Continue reading >>

Genetic Discovery May Help Better Identify Children At Risk For Type 1 Diabetes

Genetic Discovery May Help Better Identify Children At Risk For Type 1 Diabetes

Follow all of ScienceDaily's latest research news and top science headlines ! Genetic discovery may help better identify children at risk for type 1 diabetes Medical College of Georgia at Augusta University Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating or even preventing it. Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating or even preventing it. The TEDDY study's international research team has identified the new gene regions in young people who have already developed type 1 diabetes or who have started making antibodies against their insulin-producing cells, often a precursor state to the full-blown disease that leads to a lifetime of insulin therapy. Their analysis of 5,806 individuals published in the Journal of Autoimmunity also confirmed three regions already associated with one of those related conditions. "We want to build a more precise profile of who will get this disease and when," says Dr. Jin-Xiong She, director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University, principal investigator of TEDDY's Georgia/Florida site and the study's corresponding author. In keeping with their theory that two subtypes of type 1 diabetes will become clear from longitudinal studies of those at risk, the international TEDDY team also found different chromosomal regions were associated with which autoantibody shows up first in a patient, a sign his immune system is turning on h Continue reading >>

Genetics & Diabetes : What's Your Risk?

Genetics & Diabetes : What's Your Risk?

A school nurse anxiously wants to know if there is a reason why several children from her small grade school have been diagnosed with type 1 (juvenile onset) diabetes. Is it an epidemic? Will there be more cases? Is a recent chicken pox outbreak to blame? A man in his 50s develops type 2 diabetes. His mother developed diabetes in her 60s. Should this man's brother and sister be concerned, too? What about his children's chances of developing diabetes? A married couple wants to have children, but they are concerned because the husband has type 1 diabetes. They wonder what the risk is that their child would have diabetes. A couple has three young children. One of the children develops type 1 diabetes. There's no history of diabetes anywhere in either parent's families. Is this just a fluke? What are the chances the other children will develop diabetes? Chances are if you or a loved one have diabetes, you may wonder if you inherited it from a family member or you may be concerned that you will pass the disease on to your children. Researchers at Joslin Diabetes Center report that, while much has been learned about what genetic factors make one more susceptible to developing diabetes than another, many questions remain to be answered. While some people are more likely to get diabetes than others, and in some ways type 2 (adult onset diabetes) is simpler to track than type 1 (juvenile onset) diabetes, the pattern is not always clear. For more than 20 years researchers in the Epidemiology and Genetics Section at Joslin in Boston (Section Head Andrzej S. Krolewski, M.D., Ph.D., Senior Investigator James H. Warram, M.D., Sc.D., and colleagues) have been studying diabetes incidence and hereditary factors. They are continuing a scientific journey begun by Elliott P. Joslin, M.D., Continue reading >>

Is Diabetes Genetic? Facts About Hereditary Risk

Is Diabetes Genetic? Facts About Hereditary Risk

Diabetes is a complex set of diseases with no single cause. Genetic factors make some people more vulnerable to diabetes, particularly with the right environment. In addition, certain lifestyle factors can cause type 2 diabetes in individuals with no known family history. This complex interaction between genes, lifestyle, and environment points to the importance of taking steps to minimize individual diabetes risk. Is type 1 diabetes hereditary? Type 1 diabetes is an autoimmune disease, which means that it causes the body's immune system to attack healthy cells. It is often called juvenile diabetes because most people are diagnosed in childhood, and the condition then lasts their lifetime. Doctors used to think type 1 diabetes was wholly genetic. Newer studies have shown, however, that children develop type 1 diabetes 3 percent of the time if their mother has the condition, 5 percent of the time if their father has it, or 8 percent if a sibling has type 1 diabetes. Consequently, researchers now believe that something in the environment has to trigger type 1 diabetes. Some risk factors include: Cold weather. People develop type 1 diabetes in winter more frequently than summer. It is also more common in places with cool climates. Viruses. Researchers think some viruses might activate type 1 diabetes in people who are otherwise vulnerable. Measles, mumps, coxsackie B virus, and rotavirus have been linked to type 1 diabetes. Research suggests that people who develop type 1 diabetes may have autoimmune antibodies in their blood for many years before showing symptoms. As a result, the disease may develop over time, or something may have to activate the autoimmune antibodies for symptoms to appear. Is type 2 diabetes hereditary? Type 2 diabetes is the more common form of the d Continue reading >>

Immunologic And Genetic Factors In Type 1 Diabetes*

Immunologic And Genetic Factors In Type 1 Diabetes*

Under normal physiologic conditions, the entry of glucose into beta cells triggers the secretion of insulin (1) (Fig.1). The released insulin is carried in the blood to peripheral tissues where it binds to insulin receptors, which are members of the receptor tyrosine kinase family. This initiates a cascade of transmembrane events resulting in the uptake of glucose by cells and its metabolism into energy or storage as glycogen (2). Figure 1 Insulin release and action. Glucose enters beta cells via the glucose transporter (GLUT2) and ATP is generated by glycolysis. This results in closure of ATP-sensitive K+ channels, depolarization of the plasma membrane, and opening of voltage-dependent Ca2+ channels. The influx of Ca2+ leads to the release of insulin (1), which is carried in the bloodstream to cells throughout the body where it binds to insulin receptors. This results in autophosphorylation of insulin receptors and phosphorylation of tyrosines on a variety of cellular proteins including members of the insulin receptor substrate (IRS) family and Cbl-CAP (2). The phosphorylated proteins provide docking sites for SH2 domains of several proteins (e.g. phosphatidylinositol 3-kinase (PI(3)K); Grb2 and SHP2; and Crk) that activate different signaling pathways (dashed lines). This results in translocation of the glucose transporter (GLUT4) and uptake of glucose by the cell; alterations in glucose, lipid, and protein metabolism; and changes in gene expression and cell growth. Defects anywhere along the beta cell-peripheral tissue pathway can result in hyperglycemia, but at the clinical level there are two major forms of diabetes: type 1 diabetes, previously known as juvenile or insulin-dependent diabetes, and type 2 diabetes, previously known as adult or non-insulin-dependent d Continue reading >>

Genetics Of Type 1 Diabetes: What's Next?

Genetics Of Type 1 Diabetes: What's Next?

The discovery of the association between HLA in the major histocompatibility complex (MHC) on chromosome 6p21 with type 1 diabetes, but not with type 2 diabetes, suggested that these disease entities were of different genetic background and pathogenesis. The discovery that some individuals with diabetes had autoantibodies in their blood provided additional evidence that type 1 diabetes had an autoimmune origin. Recently, increasing knowledge of the genome, coupled with rapidly improving genotyping technology and availability of increasingly large numbers of samples, has enabled statistically robust, systematic, genome-wide examinations for discovery of loci contributing to type 1 diabetes susceptibility, including within the MHC itself. Currently, there are over 50 non-HLA regions that significantly affect the risk for type 1 diabetes (Many of these regions contain interesting, but previously unrecognized, candidate genes. A few regions contain genes of unknown function or no known annotated genes, suggesting roles for long-distance gene regulatory effects, noncoding RNAs, or unknown mechanisms. Against a background of ever-improving knowledge of the genome, particularly its transcriptional regulation, and with massive advances in sequencing, specific genes, rather than regions that impinge upon type 1 diabetes risk, will be identified soon. Here we discuss follow-up strategies for genome-wide association (GWA) studies, causality of candidate genes, and genetic association in a bioinformatics approach with the anticipation that this knowledge will permit identification of the earliest events in type 1 diabetes etiology that could be targets for intervention or biomarkers for monitoring the effects and outcomes of potential therapeutic agents. The International Type 1 Di Continue reading >>

Genetics Of Type 1 Diabetes

Genetics Of Type 1 Diabetes

In western populations, each child has a 0.3–0.4% risk of developing diabetes by the age of 20 years; the risk increases 15-fold in siblings of an affected child. Lifetime risks are more difficult to estimate, but may be about twice as high as this. Some 50% of the genetic risk of type 1 diabetes is conferred by genes in the human leucocyte antigen (HLA) region on chromosome 6. The HLA Class II susceptibility haplotypes DR4-DQ8 and DR3-DQ2 are present in 90% of children with type 1 diabetes, whereas DR15-DQ6 is associated with protection. High risk HLA haplotypes in a child with no family history of disease confer a risk similar to that of having an affected sibling (5–6%), and this risk rises rapidly if one or both haplotypes are shared with the affected sibling. The promoter region of the insulin gene on chromosome 11 contributes about 10% of genetic susceptibility. Many other genes (currently more than 40) make a minor contribution to type 1 diabetes, and several are of particular interest because they influence different aspects of immune function. Their ability to predict diabetes is, however, limited. Empirical risks By the age of 20 years, type 1 diabetes will have affected some 0.3–0.4% of children in the background population in western countries, and about 6% of siblings of childhood onset cases, giving a ratio (λs) of 15. Early-onset diabetes carries a higher familial risk, and affected fathers are more likely to transmit type 1 diabetes to their offspring than affected mothers, with risks being 6–9% and 1–3%, respectively.[1] These estimates represent the risk of diabetes development by young adult life, not the lifetime risk. The latter is not well established, and may be as high as 1% in the background population and 15% in siblings. Siblings wh Continue reading >>

Genetics Of Type 1 Diabetes

Genetics Of Type 1 Diabetes

The HLA region maps to chromosome 6p21.31. The classical HLA loci are encoded in a region of DNA approximately 4 Mb, with the class II loci at the centromeric end of the region and the class I loci at the telomeric end. The region contains >200 identified genes, over half of which are predicted to be expressed. A schematic representation of the HLA region, with T1D-relevant genes indicated, is shown in Figure 1. Only some of the HLA region genes are involved in the immune response; in particular, the genes that encode the classical HLA class I (A, B, and C) and class II (DR, DQ, and DP) antigens. Genes encoding classical HLA class I and class II antigens flank a chromosomal region that is sometimes referred to as the “class III region,” which contains some immunologically relevant genes (e.g., tumor necrosis factor [TNFA]) but no classical HLA genes. Products of loci encoding the six classical class I (A, B, and C) and class II (DR, DQ, and DP) antigens are structurally similar, cell-surface proteins that bind antigenic peptides and present them to T cells. DR-encoding genes differ from those encoding DQ and DP in two important ways. First, the DRA1 gene, which encodes the α chain of the DR molecule, is essentially monomorphic and does not require genotyping. Second, the DRB1 gene is present on all chromosomes, but additional DRB genes are present on specific haplotypes. Some of the additional DRB genes, e.g., DRB2, are pseudogenes; however, three of these (DRB3, DRB4, and DRB5) encode functional polypeptide chains that can pair with the DRA1 gene product to create a functional antigen. The role of these additional DR antigens in disease susceptibility is not yet understood. Molecules resembling the classical class I antigens are encoded in the HLA region, includin Continue reading >>

Genetic Causes Of Diabetes Mellitus Type 1

Genetic Causes Of Diabetes Mellitus Type 1

At least 20 different chromosomal regions have been linked to type 1 diabetes (T1D) susceptibility in humans, using genome screening, candidate gene testing, and studies of human homologues of mouse susceptibility genes. Responsible genes[edit] The largest contribution to the pathogenesis of Type 1 Diabetes comes from a single locus called IDDM1, which comes from several genes located in the Major histocompatibility complex on the 6p21.3 chromosome. This is believed to be responsible for at least 40% of the disease's familial aggreagation. Additionally, nearly 30% of Type I Diabetes patients are heterozygous for several HLA-DQ2 (specifically HLA-DQ2/DQ8) alleles. However, the HLA-DQ6 allele (HLA-DQA1*0102–DQB1*0602), if dominant, is responsible for partially preventing an organism from developing the disease. Therefore, these genetic features can be used to determine a patient's relative risk of developing the disease. Further discussion and research of the functional genomics of the pathogenesis of Type 1 Diabetes will be necessary in future studies in this field. See also[edit] Diabetes mellitus type 1 [edit] Continue reading >>

Type 1 Diabetes

Type 1 Diabetes

Print Overview Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone needed to allow sugar (glucose) to enter cells to produce energy. Different factors, including genetics and some viruses, may contribute to type 1 diabetes. Although type 1 diabetes usually appears during childhood or adolescence, it can develop in adults. Despite active research, type 1 diabetes has no cure. Treatment focuses on managing blood sugar levels with insulin, diet and lifestyle to prevent complications. Symptoms Type 1 diabetes signs and symptoms can appear relatively suddenly and may include: Increased thirst Frequent urination Bed-wetting in children who previously didn't wet the bed during the night Extreme hunger Unintended weight loss Irritability and other mood changes Fatigue and weakness Blurred vision When to see a doctor Consult your doctor if you notice any of the above signs and symptoms in you or your child. Causes The exact cause of type 1 diabetes is unknown. Usually, the body's own immune system — which normally fights harmful bacteria and viruses — mistakenly destroys the insulin-producing (islet, or islets of Langerhans) cells in the pancreas. Other possible causes include: Genetics Exposure to viruses and other environmental factors The role of insulin Once a significant number of islet cells are destroyed, you'll produce little or no insulin. Insulin is a hormone that comes from a gland situated behind and below the stomach (pancreas). The pancreas secretes insulin into the bloodstream. Insulin circulates, allowing sugar to enter your cells. Insulin lowers the amount of sugar in your bloodstream. As your blood sugar level drops, so does the secre Continue reading >>

Genetics Of Type 1 Diabetes Mellitus

Genetics Of Type 1 Diabetes Mellitus

Genes and Immunity volume 3, pages 235249 (2002) This work was in part supported by the EU BioMed 2 Programme (grant no. BMH4CT972311), Novo Nordisk A/S, The Danish Diabetes Association, and the DANDY Foundation. Support from the Juvenile Diabetes Foundation International is also acknowledged. At least 20 different chromosomal regions have been linked to type 1 diabetes (T1D) susceptibility in humans, using genome screening, candidate gene testing, and studies of human homologues of mouse susceptibility genes. The largest contribution from a single locus (IDDM1) comes from several genes located in the MHC complex on chromosome 6p21.3, accounting for at least 40% of the familial aggregation of this disease. Approximately 30% of T1D patients are heterozygous for HLA-DQA1*0501DQB1*0201/DQA1*0301DQB1*0302 alleles (formerly referred to as HLA-DR3/4 and for simplification usually shortened to HLA-DQ2/DQ8), and a particular HLA-DQ6 molecule (HLA-DQA1*0102DQB1*0602) is associated with dominant protection from the disease. There is evidence that certain residues important for structure and function of both HLA-DQ and DR peptide-binding pockets determine disease susceptibility and resistance. Independent confirmation of the IDDM2 locus on chromosome 11p15.5 has been achieved in both case-control and family-based studies, whereas associations with the other potential IDDM loci have not always been replicated. Several possibilities to explain these variable results from different studies are discussed, and a key factor affecting both linkage and association studies is that the genetic basis of T1D susceptibility may differ between ethnic groups. Some future strategies to address these problems are proposed. These include increasing the sample size in homogenous ethnic groups, high Continue reading >>

Is Type 1 Diabetes Genetic/hereditary? | Causes & Treatment - Dlife

Is Type 1 Diabetes Genetic/hereditary? | Causes & Treatment - Dlife

When left uncontrolled, high blood sugar can also cause other complications, affecting the eyes, nerves, kidneys, and cardiovascular system.[1], [4] The difference between type 1 and type 2 diabetes is that in type 1, the body does not produce insulin at all; this is why it is called insulin dependent diabetes. In type 2 diabetes, the body produces insulin but the cells are not able to utilize the insulin produced; this is why it is commonly referred to as insulin resistant diabetes. Over time, the bodys cells can develop insulin resistance in type 1 diabetes, too.[1],[5] Diabetes is diagnosed by testing the level of blood sugar or A1C (glycated hemoglobin). An A1C reading measures the three-month average plasma glucose concentration in the blood. Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies (a type of protein produced by an individuals immune system directed against one or more of the individuals own proteins).[6],[7] When specific autoantibodies are found, a doctor can make the diagnosis of type 1 diabetes. Type 1 diabetes is a rarer form of diabetes than type 2. Type 1 diabetes accounts for only five to 10 percent of all diabetes cases. Although it can occur at any age, it is more common in children and adolescents less than 15 years of age. This is why the condition was previously coined juvenile diabetes.[8],[9] The occurrence is similar in men and women, although in children it is more common in girls. Type 1 diabetes most commonly occurs during puberty. Because girls typically enter puberty earlier than boys, the condition is often diagnosed earlier in girls. After puberty, the incidence rate drops in women but continues to occur in men between the ages of 29 and 35. More than 500,000 children are currently livin Continue reading >>

Genetics And Type 1 Diabetes

Genetics And Type 1 Diabetes

If you have type 1 diabetes, you might wonder if your child would get it, too. Or if one of your parents has it, what it means for you. Your genes definitely play a role in type 1, a less common form of diabetes that’s often diagnosed in children and young adults. But they’re not the whole story. Like much in life, it’s a mix of nature and nurture. Your environment, from where you grow up to the foods you eat, also matters. Researchers don’t know exactly how -- and how much -- all those things affect your chances of getting the disease. Your genes set the stage, but you can’t be certain how it'll all play out. There’s no diabetes gene that gets turned on or off to give you type 1. Instead, a bunch of them play a role, including a dozen or so that have the biggest say: the HLA genes. They make proteins your immune system uses to keep you healthy. Since type 1 diabetes is an autoimmune disease -- your body destroys the cells that make insulin -- it makes sense that HLA genes are front and center. There are thousands of versions of them in the human gene pool. Which ones you get from your parents affect your chances of diabetes in a big way. Some make you more likely to get it, while others can help protect you from it. You have type 1 if your body makes little or no insulin, a hormone that helps your body turn sugar into energy. Certain genes are more common in one group of people than in another. That’s why race and ethnicity affect things, too. For example, white people are more likely to have type 1 diabetes than others. But even if you have genes that make you more likely to get type 1, that doesn’t mean you definitely will. Even with identical twins -- who have the same exact genes -- sometimes one gets it and the other doesn’t. That’s where the e Continue reading >>

Diabetes Mellitus Type 1 Inheritance

Diabetes Mellitus Type 1 Inheritance

Type 1 diabetes is an inherited condition and individuals with a first degree relative who has the condition are at an increased risk of developing the condition. Details regarding the risk of inheriting type 1 diabetes are given below: In men with type 1 diabetes, the risk of their child also developing the condition is one in 17. In women with type 1 diabetes who have their baby before the age of 25, the risk of the child developing the condition is one in 25. If she has her baby after the age of 25, the risk falls to 1 in 100. If both parents have type 1 diabetes, the risk of the condition developing in offspring varies between 1 in 4 and 1 in 10. The risks are somewhat increased if one of the parents developed type 1 diabetes before the age of 11. Around 1 in 7 people with type 1 diabetes suffer from a condition called type 2 polyglandular autoimmune syndrome and these individuals have parathyroid and adrenal gland disorders in addition to type 1 diabetes. If one of the parents has type 2 polyglandular autoimmune syndrome, the risk that the child will inherit the condition, including type 1 diabetes, is 50%. Genes associated with type 1 diabetes Some genes have repeatedly been identified in people with type 1 diabetes. Among white individuals, examples of such genes include the HLA-DR3 or HLA-DR4 genes. Carrying these genes raises the risk that offspring will inherit type 1 diabetes. Children born with the HLADR3/4-DQ8 genotype make up nearly 50% of all children who develop type 1 diabetes before they are 5 years of age. Some studies on other ethnic groups have shown that similar risks are associated with the HLA-DR7 genotype among African Americans and with the HLA-DR9 gene among Japanese individuals. Genetic studies have also located HLA class II genes at 6p21 and Continue reading >>

Genetic Factors In Type 1 Diabetes - The Genetic Landscape Of Diabetes - Ncbi Bookshelf

Genetic Factors In Type 1 Diabetes - The Genetic Landscape Of Diabetes - Ncbi Bookshelf

Location of INS on the human genome. INS maps to chromosome 11, approximately between 2144 and 2148kilobases (kb). Click on the figure or here for a current and interactive view of the locationof INS in the human genome. Note: this figure was created (more...) C-peptide is secreted in equal amounts to insulin, but it has long been thoughtthat it has no biological role. However, in diabetic rats C-peptide has beenshown to reduce the dysfunction of blood vessels and the nervous system that iscommon in diabetes ( 1 ). C-peptidecontains the greatest variation among species, whereas regions of insulin thatbind to the insulin receptor are highly conserved. Several single nucleotide polymorphisms ( SNPs ) have been found within the INS gene, none (at the time ofwriting) of which cause non-synonymous amino acid changes in the mature protein(see the allelic variants that are known to be associated with disease). A BLAST search using human proinsulin precursor as a query findsproteins in 107 different species, which are all metazoans apart from threeplants and one bacterium. However, potential true homologous genes have thus far been identified only in the mouseand rat. IDDM2 and Diabetes: Digest of Recent Articles For a more complete list of research articles on INS and diabetes, search PubMed. The IDDM2 locus contributes about 10% toward type 1 diabetes susceptibility( 2 ). The "risk area" of this locusis localized to a region flanking the insulin gene that contains a shortsequence of DNA that is repeated many times ( 3 , 4 ). The repeats are found0.5 kb upstream from the site where transcription of INS begins. Because therepeated sequences follow one behind the other (in tandem) and because thenumber of repeats varies between individuals, this phenomenon is called variablenum Continue reading >>

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