The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.

Autor: Alharbi AE; Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah, Saudi Arabia. Electronic address: aebharbi@taibahu.edu.sa., Ahmad MS; Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom., Damanhouri ZA; Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Mosli H; Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Yaghmour KA; Family Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Refai F; Department of Pathology, King Abdulaziz University and King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Issa NM; Department of Medical Genetics, Faculty of Medicine, King Abdul-Aziz University, Saudi Arabia; Department of Human Genetics, Medical Research Institute, Alexandria University, Egypt., Alkreathy HM; Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: halkreathy@kau.edu.sa.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 Nov 15; Vol. 927, pp. 148648. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1016/j.gene.2024.148648
Abstrakt: Purpose: To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population.
Materials/methods: 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants.
Results: Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes.
Conclusion: The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: