Gene Inheritance and Gene Mutation to Diabetes


The high rates of mortality associated with the development and complications of two types of diabetes mellitus are causing practitioners to pay close attention to determining the causes of these disorders, focusing on genetics. According to the results of recent studies, researchers have stated that genetic components are related to the development of not only insulin-dependent type 1 diabetes (T1D) but also non-insulin dependent type 2 diabetes (T2D; Nussbaum, McInnes, & Willard, 2007; Pociot & Lernmark, 2016). The purpose of this report is to describe possible chromosomal analysis that can be applied in cases of T1D and T2D, present the causes of diabetes mellitus, describe the disorder in terms of the type of inheritance, focus on practical implications and patient education, and analyze the aspect of gene mutation.

Indications for and Usefulness of Chromosomal Analysis

Chromosomal analysis conducted for the purpose of determining a predisposition for diabetes mellitus in patients is generally typical in cases of T1D. When patients are diagnosed with having autoantibodies to insulin and high levels of C-peptide and GAD65, as well as tyrosine phosphatases IA-2 and IA-2b, these aspects contribute to a determination of diabetes with the focus on its clinical course (Tallapragada, Bhaskar, & Chandak, 2015). According to Pociot and Lernmark (2016), “the larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes” (p. 2331). Much attention should be paid to identifying any genetic predisposition with the help of chromosomal analysis.

The key task in conducting a chromosomal analysis that can indicate the presence of T1D is a focus on determining specific HLA-DR3-DQ2 and HLA-DR4-DQ8 haplotypes, where HLA is the human leukocyte antigen (Pociot & Lernmark, 2016). It is also important to note that T1D and T2D differ in referring to “particular alleles at the major histocompatibility complex,” or MHC, a group of genes in chromosome 6 that can be different in length because of various haplotypes (Nussbaum et al., 2007, p. 163). According to Precechtelova, Borsanyiova, Sarmirova, and Bopegamage (2014), “the HLA-DR????1∗03:01 haplotypes carrying HLA-DR????3∗02:02 alleles showed a higher risk than HLA-DR????1∗03:01 haplotypes carrying DR????3∗01:01 in DR????1∗03:01/∗03:01 homozygotes with two DR????3∗01:01 alleles” in contributing to the development of T1D (p. 2). Therefore, chromosomal analysis is required to determine the specific genes that affect the progress of the disorder.

However, one problem is that in the first stages of developing T1D, no symptoms may be present in spite of β-cell autoimmunity. Therefore, conducting chromosomal analysis for members of a family with a history of T1D is important in terms of prevention and ability to address the development of the disease, measuring β-cell autoimmunity, and starting the treatment in the early stages (Precechtelova et al., 2014). In this context, researchers and practitioners should focus on studying the HLA region of the 6p21 chromosome in order to discover the functional genes that influence the progress of T1D.

The Causes of Diabetes Mellitus

While the causes for different types of diabetes mellitus vary, it is also critical to point out that the number of available studies is currently limited, and more research is still required in this field. T1D is usually viewed as a result of genetic factors and caused by the autoimmune destruction of beta cells in the pancreas that prevents insulin secretion. However, recent studies on the topic have also supported the assumption that the causes of T1D are more complex and are associated with a combination of both genetic and environmental factors, including viruses (Pociot & Lernmark, 2016; Tallapragada et al., 2015). From this viewpoint, genetic predisposition means that major histocompatibility complex class II haplotypes are involved in the process of provoking autoimmune responses. However, the role of environmental factors in causing diabetes has drawn more attention in studies and experiments because “there is currently a 3% annual increase in incidence, which cannot be explained by genetic predisposition” (Christoffersson, Rodriguez-Calvo, & Von Herrath, 2016, p. 2). It is also necessary to state that environmental factors mainly provoke T2D.

The general cause of T2D is related to insulin resistance influenced by metabolic changes and high glucose levels that can be associated with overweight and obesity. Monogenic diabetes also requires consideration, in addition to polygenic T1D and T2D; although it is rarely observed in people, its causes need to be examined in detail. In this context, researchers are also studying maturity-onset diabetes of the young (Tallapragada et al., 2015). Thus, a modern tendency in research on diabetes is to study its polygenic T1D and T2D forms and understand what genes and environmental factors in combination can provoke the progress of these two different types of diabetes, as well as to what extent.

Diabetes Mellitus: Gene Inheritance, Practice Implications, and Patient Education

For T1D and T2D, polygenic or complex gene inheritance is typical. While focusing on types of diabetes, it is possible to state that primarily maturity-onset diabetes of the young is characterized by monogenic or single-gene inheritance. In most cases, the type of inheritance is described as autosomal dominant or recessive (Tallapragada et al., 2015). As a result, depending on the gene inheritance type, this disorder is characterized as heterogeneous in terms of its nature or etiology. Researchers have stated that monogenic diabetes is diagnosed more rarely than T1D and T2D (Tallapragada et al., 2015). While diagnosing the presence of diabetes and focusing on its type, it is important to examine whether the observed type of diabetes is polygenic or monogenic, as it is in the case of maturity-onset diabetes of the young, because this aspect directly influences the treatment plan for the patient and the related clinical course of the disease (Stein, Maloney, & Pollin, 2014). Therefore, the problem of diagnosing monogenic or polygenic diabetes should be discussed in the context of certain considerations for practice, as well as patient education.

The treatment of T1D, T2D, and maturity-onset diabetes of the young differ significantly because of their genetic nature. According to Stein et al. (2014), “94% of children and adolescents with the most common forms of monogenic diabetes (maturity onset diabetes of the young, or MODY) were misdiagnosed, mostly as T1DM or T2DM, and 76% were receiving the wrong treatment” while following the results of a study conducted in 2013 (p. 57). The problem is that much attention should be paid to glycemic control, depending on the type of diabetes, and therapy is determined according to the genetic nature of the disorder. Referring to the example of T1D, Christoffersson et al. (2016) stated that “the key to understanding the initial autoimmune events in T1D will be to know why beta cells upregulate MHC molecules and what controls the initial lymphocytic infiltration of the islets” (p. 5). These aspects depend on the polygenic nature of T1D, and decisions related to the treatment plan and the dosage of insulin are usually based on the results of tests supporting the fact that this particular type of diabetes is present.

In this context, patient education is also important to guarantee positive outcomes for individuals. Health-care practitioners should work to improve the recognition of different types of diabetes in patients in order to help the latter understand the causes of the disorder and risk factors (genetics, obesity, and age, among others), follow the most appropriate treatment plans, and recognize the difference between polygenic and the rarer monogenic diabetes (Stein et al., 2014). Additional education for patients and information about possibilities for contacting genetic counselors can aid in coping with the symptoms of the disease.

Analysis of the Gene Mutation in Relation to Diabetes Mellitus

T1D develops as a result of an inherited mutation of genes; in comparison, T2D is not typically associated with the mutation of genes, but it can develop depending on a genetic predisposition in the family. However, it is important to note that even the development of T1D is not based on genetic factors only, and environmental triggers are important in this process. T1D can progress as a result of mutations in the HLA region of the 6p21 chromosome: HLA-DQA1, HLA-DRB1, and HLA-DQB1 (Pociot & Lernmark, 2016). These genes are responsible for causing the immune system to identify proteins produced by viruses or bacteria in order to protect the organism from this type of invasion.

When a mutation in HLA-DQA1, HLA-DRB1, and HLA-DQB1 is observed, an autoimmune disorder associated with attacking the body’s own cells and proteins develops. Changes in HLA-DQA1, HLA-DRB1, and HLA-DQB1 lead to suppressing specific beta cells that participate in producing insulin. Such a mutation in genes is inherited, and the disease develops following these stages: the gene mutation, triggering of the response of the immune system and the impact of environmental factors, and interactions with other genes in the pancreas (Precechtelova et al., 2014). Researchers have viewed the determined variations of haplotypes as risky for developing T1D. However, such mutation in certain genes accounts for only half of the factors provoking the development of T1D, and the other half are associated with environmental influences, as well as changes or mutations in other genes.


This paper has discussed the genetics of diabetes mellitus with reference to differences in the development of the polygenic and monogenic types of this disorder. Diabetes continues to exhibit a high prevalence in the United States and around the globe, and this fact is leading researchers and practitioners to pay more attention to studying the nature and causes of this disease. Currently, the actual causes of diabetes mellitus have not been clearly delineated, and researchers have supposed that a combination of genetic and environmental factors influences the development of the disease as has been shown in the case of T1D. However, genetic predisposition does not play a key role in influencing the development of T2D. Moreover, the appearance and progress of monogenic types of diabetes differ from those observed in polygenic varieties, to which T1D and T2D belong. As a result, it is important to state that gene inheritance and gene mutation as they relate to diabetes need to be studied in detail to propose the most effective methods of diagnosing and treating patients, depending on chromosomal analysis.


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Precechtelova, J., Borsanyiova, M., Sarmirova, S., & Bopegamage, S. (2014). Type I diabetes mellitus: Genetic factors and presumptive enteroviral etiology or protection. Journal of Pathogens, 2014, 1-22.

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