Transcript 1.JOSTA_AL-EITAN_7_22_2015 V2x

Utilizing Science & Technology and Innovation
for Development
A Genome Wide Association Study for Type 2
Diabetes Susceptibility Gene and Treatment in
Jordanian Population of Arab Descent
Marriott Hotel- Amman, August 13th, 2015
Project Team
•
Principle Investigator: Dr. Laith AL-Eitan/Jordan University of Science
and Technology/Biotechnology and Genetic Department /Jordan
•
Co-Investigator: Dr. Motasem Ismail/ Molecular Biology and Genetics
Laboratory/United Arab Emirates
•
Co-Investigator: Dr. Basima Almoman/Jordan University of Science and
Technology/Clinical Pharmacy Department /Jordan
•
Co-Investigator: Dr. Nesreen Saadeh/Jordan University of Science and
Technology/Internal Medicine Department/Department /Jordan
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Co-Investigator: Dr. Rami Alkhatib /Jordan University of Science and
Technology/Biotechnology and Genetic Department /Jordan
•
Co-Investigator: Dr. Nour Abdo/ Public Health/ Jordan University of
Science and Technology/Jordan
Brief Description
 The prevalence of Type 2 Diabetes (T2D) in the Jordanian
Population is steadily increasing, posing a major public health
problem.
 In T2D treatment management, Metformin is a safe and effective first line
in type 2 diabetes (T2D) therapy.
 Recent pharmacogenomic (PGx) studies indicate that genetic
polymorphisms of drug-metabolizing enzymes and transporters should be
taken into consideration.
Justifications
To date, no genome wide screen genetic factors of Type 2 Diabetes
among the Jordanian population nor any other Arab populations.
Towards this, the first Genome Wide Association Study in Jordanian
population of Arab origin will be performed using Illumina's Human
660W-Quad-BeadChip.
Work in Caucasians has previously defined genetic susceptibility
regions on Chromosomes 3, 6, 8, 9, 10, 11, 16, and 17 for diabetes and
its treatment.
To the best of our knowledge, this will be the first GWAS study to
examine the relationship between these polymorphisms of interest
within multiple genes and their relation with metformin response and
efficacy in this ethnic group, and with the clinical status with a sample
from Jordan.
Objectives
The main Objectives are:
 To measure genetic ancestry (DNA profiling) in the Jordanian
Population of Arab population using genome-wide Single Nucleotide
Polymorphism (SNP) arrays.
 To study specific diseases that are
common to populations of this region
such as Type 2 Diabetes (T2D).
 To detect genes influencing susceptibility to T2D and its treatment in
Jordanian population of Arab descent.22
Scope of work/Duration
Estimated Budget
Scope of work:
This Research proposal has three directions and its aims as following:
 Conducting Genome wide association study (GWAS) using a casecontrol based association test using the Illumina Human 660 Quad
chip array and Luminex chip array
 Identifying factors that result in obesity, and its association with T2D
by conducting a Genome-Wide Association Study (GWAS) and
specifically assessing genetic associations with "Body Mass Index"
(BMI) and "Waist Circumference" (WC).
 Evaluating and identifying factors that will be associated with
responsiveness to treatment for certain drug such as metformin and the
clinical status.
Duration: 36 months (each scope: 12 months)
Estimated Budget : 166,000 JD
Methodology of Implementation
 Blood samples will be collected from diabetic patients of Arab
descent and healthy controls from ethnically homogenous
population of Arab descent.
 DNA sample will be extracted according to the standard method
using specialized kit.
 A genome wide association study (GWAS) using the Illumina
Human 660 Quad chip array and Luminex chip array will be
conducted.
 The patients’ data and their related genotyping results will be coded
and entered into SPSS (version 19).
 Haplotype analysis will be performed using Haploview® software
(version 4.2). Permutation (n=100,000) adjustment for multiple
testing will be performed in Haploview (Barrett et al., 2005).
Expected output
 Highlighting for the first time the genetic structure variations
in type 2 Diabetic patients in Arab descent from sample from
Jordan.
 A better understanding for the role of PGx in response to
metformin therapy and treatment efficacy.
 Facilitating the integration of PGx into routine practice in the
field of diabetes care as preliminary step to assist the
introduction of personalized medicine.
 Allowing the study of specific diseases that are common to
populations of this region such as T2D
Impact
 If genetic profiling could be used Successfully to identify
high-risk individuals, this would result in substantial benefits
to both individuals and society.
 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.
 This would result in substantial improvements in quality of
life for affected individuals and a reduction in healthcare
costs.
Sustainability
 Basically, pharmacogenetic encompasses the involvement of
genes in an individual's response to drugs.
Sustainability
 The field of pharmacogenetic covers a vast area including basic drug
discovery research, the genetic basis of pharmacokinetics and
pharmacodynamics, new drug development, patient genetic testing and
clinical patient management.
 Ultimately, the development or sustainability outcome of this project may be
to predict a patient's genetic response to a specific drug as a means of
delivering the best possible medical treatment for patients in the future
according to the personal genetic level (Personalized Medicine). By
predicting the drug response of an individual in this project, it will be
possible to increase the success of therapies and reduce the incidence of
adverse side effects.
Action Plan
Stage # 1: Ordering Reagents, Kits, consumables, instruments:
Schedule: After 5 months after the proposal acceptance and receiving the funds. This stage will
include the literature Work as well.
Project Direction A: A Genome Wide Search for Type 2 Diabetes Susceptibility Genes in
Jordanian population of Arab decent
Stage 1: Collecting blood samples and clinical data (Clinical data form attached) from healthy
individuals and T2DM patients
Stage 2: Extracting DNA from both subjects (T2DM patients and healthy indivuals) and
quantifying the DNA concentration and assessing the DNA quality using a NanoDrop 1000®
spectrophotometer
Stage 3: Building a clean data sets for both clinical data and DNA samples for both subjects
Action Plan
Schedule: 1 year after the proposal acceptance and receiving the funds and Reagents, Kits,
Consumables
Stage 4: Conducting GWAS analysis either at Princess Haya Biotechnology Centre or sending
the samples overseas for analysis
Schedule: 4 months after the clean data sets established
Stage 5: Standard biological molecular methods such as Taqman® SNP genotyping assay, DNA
sequencing using Genetic Analyser 310, and restriction fragment length polymorphism (RFLP)
will be employed for genotyping in the current study to confirm the quality of the Genome Wide
Scan Genotyping technology for certain SNPs within specific genes.
Action Plan
Schedule: 10 months after DNA extraction and building a clean DNA data
set.
Stage 6: Data, bioinformatics and statistical analysis
Stage 7: Writing manuscript for publication
Schedule: 3 months following the genome wide scan analysis and SNPs
confirmations
Action Plan
Project Direction B: A Genome-Wide Association Study Examining
Obese Factors in Jordanian population of Arab Decent with a History
of Type 2 Diabetes
Stage 1: Data, bioinformatics and statistical analysis and
interpretation.
Stage 2: Writing manuscript for publication.
Schedule: 3 months following the data and bioinformatics analysis
Action Plan
Project Directions C: A Pharmacogenetic Approach Using Genome Wide
Association Study to Search for Type 2 Diabetes Susceptibility Genes and
Treatment
Stage 1: Data, bioinformatics and statistical analysis and interpretation.
Stage 2: Writing manuscript for publication.
Schedule: 3 months following the data and bioinformatics analysis