Genetic research studies examine genes, the instructions in our DNA which control how the body is built. Genetic diseases are often inherited and can affect multiple members of a family. The study of genes can lead to a better understanding of, and new treatments for, human diseases.
A phenotypic approach in subclassifying the heterogeneity of diabetes in Emirati population.
- Diabetes Mellitus (DM) is conventionally classified in to Type 1 (T1D), Type 2 (T2D), secondary and monogenic forms. Considerable heterogeneity exists within these groups and these broad classifications are not themselves sufficiently accurate for risk stratification of microvascular and macrovascular complications at diagnosis.
- Recent studies proposed that a more detailed sub-classification of diabetes type at diagnosis may provide valuable insights into complication risk and enable both more effective individualization of treatment, and more efficient use of healthcare resources.
- These proposed diabetes subgroups have not been validated in Middle Eastern population.
Inclisiran for the treatment of hypercholesterolemia in clinical practice.
- Inclisiran is the first clinically available small interfering RNA (siRNA)-based treatment for hypercholesterolemia. Inclisiran acts by inhibiting PCSK9 synthesis and is indicated for management of elevated LDL-C and TC in patients with cardiovascular disease (CVD) or familial hyperlipidaemia (FH) and / or with statin-intolerance.
- Inclisiran requires less frequent dosing than alternative therapies and has been shown to reduce LDL-C levels by more than 50% with a single dose (284 mg), administered initially at 3 months, followed by every 6 months, whereas statins required a daily oral dose administration and PCSK9-I every two to four weeks.
- In general, new therapies are developed and validated in Northern European and North American populations, but data regarding effectiveness and safety in Arab populations are lacking.
- The proposed study will improve the understanding of the clinical utility of Inclisiran in Emiratis.
Clinical and Research Genetics Project
- The primary purpose of the study is to genetically define undiagnosed genetic conditions and identify novel disease-causing genes and/or mutations from specific clinical cases using genetic sequencing (such as next generation sequencing (NGS) that include multiple gene panels, whole exome/genome sequencing (WES/WGS), and mRNA sequencing) methodologies in individuals and/or families across the United Arab Emirates.
- Current study will target both paediatric and adult participants who underwent clinically available genetic testing and had negative test results yet considered highly likely to have genetic condition/mutations by their treating physician.
- It is hoped that, through this study, individual participants and/or their families will receive a clear genetic basis for their specific condition, identifying disease-causing genes/mutations, which may lead to improvements in diagnostics, treatment and care in the future.
The Real World Experience Of Evolocumab for treatment of Hyperlipidemia on the UAE Population
- The administration of Evolocumab as being a mono-therapy or with other lipid lowering drugs reduces the LDL-C effectively by up to 60% in patients with or without familial hypercholesterolemia (FH), diabetes, or coronary artery disease (CAD).
- Data regarding the safety and effectiveness of PCSK9 inhibitor in MENA region is lacking. We sought to investigate the effect of Evolocumab on lipid profile in Emirati population.
- 183 patients from Jan 2017- Nov 2020 were identified, attending ICLDC and were treated with Evolocumab and included in the study.
- Study designed in order to analyse the genetic architecture of Emirati population diagnosed with type-2 Diabetes and identify population pharmacogenomics responses to diabetes medication
- 156 index cases have been recruited, together with 87 parental samples and 502 singletons
- Analysis (including genotyping) to be completed on samples from 2,700 participants
Urinary C-peptide to Creatinine Ratio (UCPCR)
- The body makes C-peptide as a by-product of the manufacture of insulin, the glucose-lowering hormone. Measuring the amount of C-peptide in the urine (UCPCR) can tell us how much insulin the pancreas is able to make.
- This study was undertaken in order to determine the usefulness of UCPCR to identify different causes of Diabetes Mellitus, including Type 1 Diabetes, Type 2 Diabetes and Maturity Onset Diabetes of the Young (MODY)
- Preliminary results support the need for Emirati-specific UCPCR and MODY risk calculator parameters to be implemented. Furthermore, prevalence of MODY in the Emirati population seems to differ from the suggested prevalence in the European population
- We are extending the study to look at other genetic markers which can be used to tell one type of diabetes from another, improving the accuracy of diagnosis and initial treatment of people with Diabetes Mellitus.
Genetic Causes of Familial Hypercholesterolaemia (FH) in the Emirati population
- Familial Hypercholesterolaemia is a common genetic disease which causes increased levels of LDL cholesterol and premature onset of arterial diseases. Identifying people with FH early allows them to be treated before the onset of symptoms and can potentially prevent heart disease and strokes.
- This study was established in order to identify how many Emirati people might have FH and potentially identify novel genes/mutations responsible for the condition
- 1612 individuals have been recruited, with genetic analysis conducted on 249 patients
- Results suggest similar incidence of mutations in canonical genes to those previously reported for other populations
- Establishment of Dyslipidaemia Registry as part of the research project
Genetic Causes of Gestational Diabetes (GDM) in the Emirati Population
- While most people with diabetes do not have a clear genetic cause, some people have an abnormality in a single gene which causes diabetes mellitus. These rare types of diabetes, known collectively as Maturity Onset Diabetes of the Young, or MODY, are treated quite differently from the more common Type 1 and Type 2 diabetes.
- Gestational Diabetes Mellitus (GDM) is high blood sugar which is diagnosed early in pregnancy and in most cases resolves following delivery.
- We want to find out how many Emirati women diagnosed with GDM actually have MODY. This will enable improvements in diagnostics, treatment and the counselling of these women.
- 452 candidate women with GDM or history of GDM have been recruited and genetic analysis has been performed on 416 candidates
Acanthosis Nigricans in the Emirati population
- Acanthosis Nigricans (AN) is a skin condition which most commonly affects people who have “insulin resistance”, a feature of Diabetes Mellitus.
- We do not know exactly how people develop AN, or how AN is linked with Diabetes Mellitus, and so investigating the genetic basis of AN might lead to new treatments for both conditions.
- 338 people have been recruited to date
Delineation of Novel Genetic Disorders in the UAE Population
- Diseases which are likely to be caused by an abnormality in a single gene are among the most common causes of disability in people living in the UAE. However, the actual genes causing most of these diseases have not yet been identified.
- New developments in gene sequencing give us the opportunity to search for and diagnose these genetic diseases and, by understanding more about the disease process, potentially develop new treatments for this rare disease and possibly much more prevalent disease sharing the same pathway.
- In collaboration with the Zayed Higher Organisation and UAE University, we are currently recruiting patients whose disease seems likely to be caused by a single gene into this study.