Precision Medicine in Diagnosis and Treatment of Type 2 Diabetes Mellitus in the United Arab Emirates

Abstract

The rate of occurrence of Type 2 Diabetes Mellitus (T2DM) has been exponentially increasing worldwide. The current management of this disease is not deeming to be sufficient and further efforts need to be placed in this regard. The conduction of genome-wide association studies (GWAS) and pharmacogenomics (PG) have unlocked unlimited potential in more efficiently assessing disease susceptibility, drug response, and disease related complications. These efforts have indicated the necessity of executing such studies to further understand the underlying genetic causes that are tailored to specific populations for a more personalized approach. The current literature on such findings is heavily dedicated to those of European, Asian, and African ancestry, indicating the lack of focus on the Arabian Peninsula. Therefore, genetic initiatives to tackling T2DM that are yet to be addressed within the United Arab Emirates (UAE) are of great necessity to ensure its inclusion in these advancements for a more enhanced disease management of T2DM.This research was an initiative for the integration of the UAE in the scientific advancements currently taking place in the genetic filed. With T2DM being a public health concern in the country, we aimed in further understand the underlying genetic implications associated with disease development in the Emirati population. A GWAS was conducted on 338 T2DM Emirati individuals where they were stratified according to diabetes-related complications experienced: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and macrovascular complications. Illumina's Infinium Exome-24 kit was used which has a total of 244,883 fixed markers where after imputation 39,840 SNPs remained for analysis. The analysis revealed the associations of various SNPs with each complication category including: rs4664229 (ACVR1C, OR=2.33; 95% CI=1.49-3.66), rs61729527 (ZFHX4, OR= 4.65; 95% CI=2.02-10.69), rs9616915 (SHANK3, OR= 0.46; 95% CI=0.29-0.71) and diabetic retinopathy, rs4802605 (GFY, OR=3.94; 95% CI=2.01-7.77), rs2273961 (NCR2, OR=3.51; 95% CI=1.87-6.60), rs4148883 (ADH4, OR= 2.52; 95% CI=1.57-4.01) and diabetic neuropathy,rs72646845(TTN, OR=38.05; 95% CI=6.45-224.40), rs113848006(PI16, OR=12.91; 95% CI=3.59-46.49), rs41272737(CROCC, OR=9.51; 95% CI=2.99-30.28) and diabetic nephropathy, rs62406032(PKHD1, OR=5.98; 95% CI= 2.49- 14.38), rs1078264(MAST1, OR=2.93; 95% CI=1.69-5.08), rs4802605(GFY, OR=3.99; 95% CI=1.96-8.11) and macrovascular complications. These findings highlighted key loci that are associated with T2DM complications that are specific to the Emirati population revealing the significance of conducting such studies. Through this, early detection methods can be developed to identify individuals at a high risk of these complications and to further elucidate the underlying mechanisms that drive their manifestations for treatment development. Even though the results of this research aided in further unravelling T2DM complications in the UAE, the results did not reach genome-wide significance. This could be due to a couple of reasons including the small samples size, the genetic drift in the MENA region, and the high interbreeding within the UAE leading to many monomorphic SNPs in this population. This allowed for the following conclusion to be made: GWAS is an excellent tool towards precision medicine but we first need to develop a more comprehensive chip that accounts for the admixture populations for it to finally be implemented in medical practices.

Date of Award	Dec 2021
Original language	American English