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

• 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.

JustificationsTo 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/DurationEstimated Budget

Scope of work: This Research proposal has three directions and its aims as following:

Conducting Genome wide association study (GWAS) using a case-control 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.

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.

Sustainability

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

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

Action Plan