An Exploration of Genes, Inheritance and Gene Therapy for Diabetes - Essay Example

AN EXPLORATION OF GENES, INHERITANCE AND GENE THERAPY FOR DIABETES An Exploration of Genes, inheritance and gene Therapy for Diabetes Gene therapy refers to the introduction of materials of genetic origin into a cell to correct or compensate for malfunctioning or abnormal genes or even synthesize beneficial proteins in ailing patients. The introduction of such a particular gene which is the DNA portion coding for s particular nucleotide is accomplished by the use of a suitable vector, mostly a nonpathogenic virus which is used as an agent of gene transfer from donor cells of desired characteristics to receiver (Naff 2005,pg.67). Scientists mostly use retroviruses although adenoviruses have also been used. In more sophisticated areas these genes have been introduced directly to cells. This is done to treat and control genetic diseases which are inherited by mendelian fashion either as sex linked autosomal dominant or autosomal recessive (Clayman 1993,pg.56). Currently gene therapy is being researched to treat diabetes which predominates among the first degree relatives of the affected. Hyperglycemic states as a result of diabetes are on the rise and studies have shown the susceptibility to becoming diabetic among first relatives of patients is very high thus indicating a correlation between genetics and diabetes (Friedman 2006,pg.65). Various combinations of genes as well as risk factors that are environmental in origin have been associated with the causation of the higher than normal glucose level in the two predominating types of diabetes. Insulin dependent diabetes tends to dominate among the young population otherwise called type II diabetes is uncommon compared to type II which is responsible for hyperglycemia in 90% of clinically diagnosed states (Friedman 2006,pg.43). Unlike the maturity onset type of diabetes (MODY) which is directly inherited resulting from rare mutations of DNA in the mitochondria, there others have a more complex genetic association that have been studied which has suggested a possibility of treatment of diabetes using gene therapy. The disease has a distribution of about 15 for every 100,000 people each in the UK which is not very different from the epidemiologic data from USA and India (Eisenbarth 2004,pg.34). The exact pattern of inheritance remains uncertain although type 1 is suggestively mendelian with a juvenile onset. Genes, which are the portions of DNA involved in the coding a protein form the functional unit of inheritance (Naff 2005,pg.82). Some syndromes always bring back to diabetes. Taking Cushing’s syndrome for instance, the excessive cortisol mobilizes metabolism of glycogen to glucose which result to diabetes. Other metabolic states that are implicate in a much similar manner includes obesity which may either be due to consuming of excess calories or genetic predisposition that increases the risk of becoming hyperglycemic. Cushing’s syndrome is likely to induce insulin resistance due to accumulation of glucose which overworks insulin receptors leading to adaptation that is characterized by reduced response. Type I diabetes on the other hand is common in Downs’s syndrome, myotonic dystrophy, Klinefelters syndrome and Huntington’s disease which have autoimmune and metabolic aspects that destroy the pancrease (Stehouwer & Schaper 2009,pg.41 There are two main types of diabetes mellitus. These are diabetes type1 which has a juvenile onset and is insulin depend and diabetes type2 occurring mostly in adults and manifesting as non-insulin dependent (Stehouwer & Schaper 2009,pg.56). Both types have different etiology and genetics that determine the type of treatment plan to be adopted. In type 1, there is an autoimmune response which destroys the insulin beta cells. It is passed on to the first degree relatives of affected for at approximately 6% rate as opposed to general population who stand only a 1% risk of developing it (Eisenbarth 2004,pg.60). This exhibits a connection between genetics and occurrence of insulin dependent diabetes. Given that the HLA II gene on chromosome 6 is altered by 20% in suffering individuals the autoimmune response is likely a result of a mutation. A transcription protein seems to be the inducer of the mutation and insulin promoter factor has been identified as one of the inducers. The genes also contribute to about 40% risk of heritability especially haplotypes DQA1*O501-DQB1*0201. Another halo type implicated is the DQA1*0301-DQB*0302 (Friedman 2006). When the central regions of these genes are prolonged more than usual, the result is increased risk to susceptibility. Furthermore, when tandems of insulin gene that is located in chromosome number 11p15.5 is non-transcribed or repeated at the 5’ area of the flanking region, juvenile diabetes occurs (Friedman 2006,pg.57). Abnormal cytotoxic T lymphocyte 4 is also inducers of the autoimmune response to beta cells. Risks from environmental exposures to DT1 are minimal and mainly as a result of some infections, particularly viral infection. The exposures to these and certain other agents may either initiate the onset or accelerate and aggravate an existent diabetic state (Friedman 2006,pg.72). Coxsakie B virus infections are common in children and commonly affect the pancrease after systemic spread (Clayman 1993,pg.55). Prospective research findings have recently shown that enteroviral infections in utero increase risk. Hypothetically, early exposures to cattle milk proteins induce immune reactions which destroy the pancrease of improperly breast fed babies. There is also a postulation that inadequate or short breast feeding time of less than 6 months increases risk since the intestinal mucosa fails to develop enough immunity to infection which mostly causes abnormal immune responses (Clayman 1993,pg.82). Type 2 diabetes on the other hand has a completely different etiology. It is found 90% of general diabetic population with an adult onset between 30 to over 60years where the glucose level of a fasting patient exceeds 70mmols and two hours after previous check (Shallenberger 2006,pg.33). Hypothetically it manifests as the 30 genotype and has been on the rise with the current incidence of obesity where physical inactivity and poor diet control seem to lead to progression in 30% of obese population (Shallenberger 2006,pg.77). According to Shallenberger (2006), genes involved include the peroxisome proliferative activator receptor (PPARy) on locus 3p25 especially the variant Pro12A1a, an allele which predominate in 98% of Caucasians. Another gene involved is ABCC8, the region that is bound to ATP for opening of sulphonyl urea site on beta cells. Mutations at this region make an individual to be at high risk of insulin resistance. Polygenic causes also include potassium channel that rectify in an inward fashion (Shallenberger 2006,pg.63). Insulin resistance is sometimes independent of weight gain and therefore idiopathic. The liver may malfunction and produce abnormal levels of glucose. Hypertension also increases the risk in a much more similar fashion as dyslipidemia in susceptible population. Furthermore, modifications of the histones in DNA and microRNAs together with DNA hyper methylation increase the chances of becoming diabetic (Stehouwer & Schaper 2009,pg.83). However, intrauterine environment can induce diabetes type 2 although the exact mechanism of causation to pregnant women is not well known. From the foregoing the research in genes associated with the metabolic state in diabetes has shown particular genes are abnormal and this has paved way to gene therapy. Since viruses have been proved suitable vectors in gene transfer, it has been possible to correct aberrations in insulin coding genes and altered genes in diabetics (Stehouwer & Schaper 2009,pg.88). The role of this therapy in diabetes involves the replacement of a defective gene or that which adapts abnormally in insulin resistance. It also includes the destruction of aberrant cell such as resistant insulin receptor gene. In type 1 diabetes, the role of gene therapy has mainly been to induce the production of beta pancreatic cells. Diabetic gene therapy was developed from the early 1970s proposal that suggested gene surgery as a means of alleviating inherited ailments. Focus of gene therapy is on the identification of the responsible genes in diabetes acquiring a treating transgene which is delivered using an appropriate vector (Lee 1993,pg.55). Proper timing of the events in the gene is observed such that regulation can be achieved to enable correct expression of desired traits. The gene targets in diabetes are that on chromosome 11 which codes for insulin and the HLA class II genes to fight autoimmunity to insulin beta cells and increase insulin production (Lee 1993,pg.62). Through gene therapy various forms of animal insulin; bovine and porcine have been modified and purified to become equivalent to human insulin in their amino acid sequence and pattern. However, the current situation in the advancement of gene therapy is hindered by high costs of the technology and is under scrutiny of various ethical viewpoints (Lee 1993,pg.77). The health care personnel and public have not yet embraced it due to lack of information on evidence based break through. In future however, the barriers will be overcome to develop gene screening to diagnose diseases and provide treatment. Monoclonal antibodies to destroy the autoimmunity antibodies are underway to treat type 1 diabetes. The quality assurance procedures are being revised to access the safety of vector introduction (Naff 2005,pg.93). The genetic information is therefore being manipulated to advance in gene therapy to target the malfunctioning genes in both type 1 and ty2 diabetes. The success of this development is hindered by a number of circumstances as discussed above but the future promises a sophisticated improvement and development that would make gene therapy successful and acceptable in the management of diabetes (Shallenberger 2006,pg.65). These efforts seek to treat the condition at gene level to correct errors that injured or transformed the beta cells to culminate to diabetes. It will also serve broadly as a genetic testing field for testing more diseases that are yet to be genetically understood. References Clayman, C. B., & American Medical Association. (1993). Genes and inheritance. Pleasantville, NY: Readers Digest. Eisenbarth, G. S. (2004). Immunology of type 1 diabetes. New York: Kluwer Academic/Plenum Publishers. Friedman, J. E. (2006). New transcription factors and their role in diabetes and therapy. Amsterdam: Elsevier. Lee, T. F. (1993). Gene future: The promise and perils of the new biology. New York: Plenum. Naff, C. F. (2005). Gene therapy. Detroit: Thomson/Gale. Shallenberger, F. (2006). The Type 2 diabetes breakthrough: A revolutionary approach to treating Type 2 diabetes. Laguna Beach, CA: Basic Health Publications. Stehouwer, C. D., & Schaper, N. (2009). Diabetes. Oxford: Clinical Pub. Read More