Diabetes as One of the Fastest Growing Debilitating Disease in the World - Research Paper Example

?2. Diabetes is currently among the fastest growing debilitating disease in the world. In year 2007 United Arab Emirates (UAE) was ranked second country in the world with in regard to prevalence of. Latest study carried out by specialist in Al Mafraq hospital sponsored by WHO revealed that 26% of UAE nationals suffer from diabetes, and that 40% of those aged 60 years and above suffer from the disease with cardiovascular (CVD) complications. To date, no research has been conducted on the implication of genetic testing, or genome wide screening for Type 2 Diabetes with CVD among UAE population nor any other Arab population. This study aims to identify patients with Type 2 Diabetes who have also developed cardiovascular disease (myocardial infarction) to measure genetic variation related to T2D with CVD on an Arab population sample in UAE using state-of-the-art technology in genome field; genome-wide Single Nucleotide Polymorphism (SNP) arrays. Our long term goal is to utilize the outcome of the study in individualization of drug therapy and diagnosis of T2D with CVD bases on the genetic profile of patients from Arab Population. This would result in substantial improvements in quality of life of the affected individuals and a reduction in healthcare costs. Identification of target genes may also lead to development of novel therapeutic modalities. Furthermore, the characteristics of Arabic population make them ideal for the genome wide study of diabetes, a complex, polygenic, multi-factorial disorder. 3. Relevance It is hoped that this proposed study will pave way in identifying susceptibility genes for the Type 2 Diabetes with CVD in UAE population moreover. It will assess if genetic profiling could be used successfully to identify high-risk individuals, this would result in substantial benefits to both individuals and society. Moreover, targeting preventive measures towards individuals with high-risk genotypes could delay the onset of disease, slow its progression, and reduce the ultimate severity of the condition. Finally, this study will lead to substantial improvements in quality of life for affected individuals and a reduction in healthcare costs and also the identification of target genes might also lead to development of novel therapeutic modalities. 4. Project Personnel Dr. Habiba alsafar is the lead investigator on this program and will dedicate 1.2 calendar months approximately 10% of her time overseeing the project. Dr. Nicolas Christoforou is a molecular-cell biologist and an academician at KUSTAR and will, he will avail essential tools in all aspects of molecular biology. He will also provide training and supervision to interns. Dr. Christoforou will dedicate 0.8 calendar months, approximately 8% of his time supervising the project. Dr. Ahsan Khandoker will dedicate 0.5 calendar months i.e. approximately 5% of his time preparing tools in the assessment of cardiac autonomic function for this study. Dr. Maher Maalouf from Industrial department in KUSTAR is planned to dedicate 0.5 calendar months approximately 5% of his time providing valuable support and consultative advice regarding statistical methods and analyses of the project KUSTAR nominees have also invited Drs. Ahmed Hasson to be a co-investigator in this study. He is a consultant Endocrinologist and chairman of Research & Medical Education from Dubai Diabetes Center in Dubai. Dr Ahmed will contribute as clinical expert, access to T2D patients with CVD and provide guidance on clinical matters. 5. Objectives and Goals This proposal present plan to initiate a seed project in the United Arab Emirates (UAE) particularly in Abu Dhabi with an aim of identification of genetic associated with Type 2 Diabetes resulting to development of cardiovascular disease (myocardial infarction) among Arabs in UAE. Furthermore, address genetic diversity in UAE providing insight into mechanisms that cause this disease. These developments could possibly lead to improved intervention and prevention programs to improve quality of life throughout UAE and individualization of drug therapy for chronic diseases based on genetic profile. Furthermore this study will provide answers to questions about issues such as: Is there an interaction risk factor between the causing gene and the complication of Type 2 Diabetes among UAE population? Possibility of identifying people who are clinically healthy but are heterozygous carriers of genetic diseases such as T2D with CVD complication? Can a genetic testing establish whether an asymptomatic person carries a mutation responsible for a future disease? Will it be possible to identify genes activated or deactivated in people before developing T2D complication? Discovery of genes role in development of CVD with T2D? Identification of people at high risk of contacting CVD complication for T2D and probable preventative measures? Possibilities of developing better treatment and prevention methods for both of diabetes upon identifying its causing gene? Why many UAE citizens develop CVD as a complication of T2D? Will it be possible to develop Arab haplotype map of the human genome in UAE? The null hypothesis of this study is that the alleles and genes in the Arabic population predisposing patients to Type 2 Diabetes with CVD are the same as those described for other populations previously studied. While the alternative hypothesis is that novel genetic factors unique to the Arabic population contribute to the pathophysiology of the disease. Regardless of the findings, data gleaned from this study will result in characterization and definition of Arabic haplotypes associated with the disease. 6. Project Description Backgrounds Type 2 Diabetes (T2D) is a group of metabolic diseases characterized by hyperglycaemia[1][2]. Several physiological processes are involved in development of diabetes [1]. These range from autoimmune destruction of ?-cells of pancreas with consequent insulin deficiency leading to abnormalities that result in resistance to insulin action. The majority diabetic cases fall into two broad etiopathogenetic categories: Type 1Diabetes (T1D) caused by an absolute deficiency of insulin secretion, and T2D caused by a combination of resistance to insulin action and an inadequate compensatory insulin secretary response. T2D accounts for 90 to 95% of those with diabetes. It was previously referred to as non-insulin dependent diabetes or adult onset diabetes [3]. It includes individuals who have insulin resistance, relative insulin deficiency, and usually need insulin treatment mainly later in the course of disease [4, 5]. The chronic hyperglycaemia resulting from diabetes is associated with long-term dysfunction, damage and eventual failure of various organs [6, 7]. These changes mainly occur due to micro and macro- vascular complications. Long-term complications of diabetes include retinopathy with potential loss of vision; nephropathy leading to chronic kidney disease; peripheral neuropathy with risk of foot ulcers, amputations and Charcot joints; and autonomic neuropathy causing gastrointestinal, genitourinary, and cardiovascular symptoms and sexual dysfunction [8_ENREF_8] In this project we are focusing on cardiovascular diseases (CVD) which is a growing cause of concern globally, mainly due to complication of Type 2 Diabetes. According to World Health Organization (WHO) statistics CVDs are the primary cause of deaths worldwide. It is estimated that more people die from CVDs annually than from any other disease. WHO further reports that in 2004, CVD was responsible for 17.1 million deaths globally. This represented 29% deaths worldwide; 7.2 million deaths were due to coronary heart disease, while stroke was associated with 5.7 million deaths. WHO estimates that by 2030, deaths due to CVD would amount to 23.6 million, most of which will have resulted from stroke and heart disease (“WHO Fact Sheet”). Considering this grim reality, comparative genomics in medical science has been widely used to identify genetic factors that cause this disease. Thus Genome wide scans to map type 2 diabetes susceptibility loci have been conducted in many different populations (2). Some of the mapped loci have been observed in multiple populations. Other regions, however, may be unique to specific populations. This may reflect underlying phenotypic heterogeneity, racial or ethnic differences in susceptibility allele frequencies, or differences in sample size, study design, and analytical methods. The disease has not been extensively studied among the Arab populations of the Middle East. Furthermore, the characteristics of Arabic population make them ideal for the study of complex, polygenic, multi-factorial disorders such as diabetes [9]. This is because this particular population is characterized by genetic homogeneity due to the tribal structure of their society, large family size and extensive consanguinity. In UAE; as well as other Arab countries; satisfactory epidemiological studies on the prevalence of Type 2 Diabetes with CVD complication are lacking. Moreover, lack of genome wide association studies leaves very little to be discussed regarding genetic prevalence of the disease in Arab countries. Therefore, there is a pending need for the development of genome wide association studies for populace of the UAE and other Arab nations. Innovation An extensive review of the literature using PubMed and Science direct revered that there are no studies which have been published on the genes causing Type 2 Diabetes with CVD complication among the UAE and Arab populations. Therefore, the proposed study will be the first genome wide screen in the Middle East focusing on identification of the genes involved in the development of CVD caused by Type 2 Diabetes among the UAE population. Thus, the completion of this important project will help prevent and identify patients predisposed to CVD as a complication of T2D in early stages of the disease. Furthermore, it will place UAE in a very high status since it would be the first Arab country to conduct a genome wide scans for T2D with CVD complication in the Arab world. Methodological Approach and Work plan In order to achieve the objectives and goals of this proposal collaboration will be established with major hospitals and diabetes centers in Abu Dhabi. Through this collaboration, demographic data of type 2 diabetes patients will be evaluated and tabulated in highly professional database. A total of 200 Saliva samples using DNA GenoTeck kit will be taken from Diabetic with CVD, Diabetic without CVD and non Diabetic (healthy) Arab patients who are between 40 to 60 years old for genotyping after their consent. Information regarding their lifestyle and family history will be also recorded for correlation with the genetics and environmental factor. Samples from healthy individuals with no family history of Type 2 Diabetes will be used as controls in the study. If we couldn’t collect 200 samples in 4 months the sample collection will expand to other emirates. Genome wide screening of the sample will be done using Human-1M chips which will be scanned on Illumina’s BeadArray™ technology. The generated data will be promptly evaluated for strategically selected markers of genetic variation, referred to as single nucleotide polymorphisms (SNPs). The association between individual SNPs and disease (Type 2 Diabetes with cardiovascular complication) trait will be analyzed using different statistical packages such as PLINK, UNPHASED and GENABEL. The proposed project will be completed within 11 months. In the first 6 months of operations, the plan will attempt to recruit between 150 and 300 participants; a modest estimate; throughout the expanded network of collaborators. Broader Impact The work proposed here-in will systematically catalogue samples and clinical data of populations of the UAE (and possibly other participants in the Arab world). It will be an invaluable resource for basic research focused on identifying genetic and environmental predispositions to disease that afflict local population of the UAE. There will be great benefits gained from the identification of genes that contribute to disease. An understanding of the etiology of disease will improve prognosis and assist in the development of cures and intervention studies. These measures will improve the quality of life of the citizens of the UAE through the provision of better health care services. Internal Benefits The Molecular laboratory at the Biomedical Department in Khalifa University will provide the following to the collaborators: Training opportunities for medical graduate, Medical doctor and students. Typically, staff transfer will be encouraged and experts from other institutions could be placed at the Khalifa University. Double badge opportunities for students with reputable Universities will be explored and adjunct positions for staff will be established. Two interns will be hired in the project with undergraduate or postgraduate qualification. These interns will be given hand on training of genotyping techniques to be used in the project. Regional Benefits The boarders currently separating nations of the Arab world are political boundaries. These do not account for the distribution of the Arab who can be found scattered throughout the middle-east. The benefits from the discoveries made through this project will extend to all nations throughout this region. Despite the project initiative uniqueness in that it will focus on Arabs; the concept of GWAS study is not novel. Consequently, other research groups in the region will be contemplating establishment of similar initiatives. An essential mandate of this project will be to promote cooperative research throughout the region. Successful implementation of this plan will see this inaugural Arab-based epidemiological resource based in the UAE. International Benefits The success of this project will not only attract regional attention but also result in fostering cooperative R&D links with other groups in Australia, Asia, Europe and North America. Genomic studies since the 1990s have been based on cooperative efforts of the international community. The design of this study requires cooperative R&D as the identification of disease genes requires both the study of diversity, which is the variation between disease and normal as well as variation that explains ethnic differences. This study will improve the global competitiveness of Arab Genomic research. Justification for Budget DIRECT COST The 2 interns working on the project, will be provided with a honorarium as their salary (AED 1620 per month) when collecting data and samples throughout the UAE. Dr. Habiba Al Safar is the lead investigator on this program and will devote 1.2 calendar months approximately 10% of her time overseeing the project. Dr. Nicolas Christoforou is the senior Co-investigator on this project and will offer 0.8 calendar months approximately 8% of his time supervising the project. Dr. Ahsan is the Co-investigator on this project and will dedicate 0.5 calendar months approximately 5% of his time overseeing the project. Dr. Mahar is the Co-investigator on this project and will give 0.6 calendar months approximately 6% of his time managing the statistical approach of this project. MATERIALS & CONSUMABLES Quotations for DNA kits to isolate DNA from the samples and Illumina Chip bead array has been obtained and appended to this application. We are only able to estimate a budget for genotyping 150 individuals. TRAVEL As indicated, the study will include visits to other centers throughout the UAE. A provision for travel has been estimated at AED 800 per month and AED 8000 for attending any regional meeting or conferences which includes registration fees, accommodation and food. OTHERS The budget allows for a modest amount of AED 18,000 for any miscellaneous expenditure such as publication fees, purchasing journals or books related to this project. External Support There is an increasing range of competitive research grants being offered within the UAE. This project is planned as a collaborative effort of centers and Universities across the UAE with conducting a GWAS being a focal point for biomedical research in the region. The faculty at KUSTAR will seek external funds to support this project in screening 1,000 individuals who suffers from Type 2 Diabetes with CVD complication. These external funds will be obtained through national fund agencies such as Emirates Foundation, Abdul Latif Jameel Foundation, and National research foundation. Moreover, there are many international research grants applicable to faculties working in the UAE such as National Science Foundation and Qatar National Research Fund which will be contacted to seek external support. In addition, this proposal will be sent to various International biotechnology companies who frequently support and fund such project by providing material and consumables such as DNA kits. Read More