Association between the TP53 Arg72Pro (rs1042522) Polymorphism and Type 2 Diabetes Mellitus: Implications for Molecular Imaging Biomarkers
- 1 ARUA Centre of Excellence for Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya
- 2 Department of Biomedical Laboratory Sciences, INES Ruhengeri-Institute of Applied Sciences, Ruhengeri, Rwanda
- 3 ARUA Centre of Excellence for Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya
- 4 ARUA Centre of Excellence for Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya
- 5 ARUA Centre of Excellence for Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya
- 6 Department of Biochemistry, Madras Medical Mission, Chennai, Tamilnadu State, India
- 7 Department of Pathology, Government Medical College, Rajasthan University of Health Sciences, Jaipur, Rajasthan State, India
- 8 Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion. Genetic factors, including variations in the TP53 gene, may influence metabolic pathways linked to disease progression. The p53 protein regulates apoptosis, DNA repair, and cellular metabolism, suggesting potential relevance as a molecular biomarker in imaging-based disease assessment. A hospital-based preliminary cross-sectional study was conducted from June to August 2024 among participants recruited at Ruhengeri Level Two Teaching Hospital and Rwamagana Level Two Teaching Hospital, Rwanda, while molecular analyses were performed at the Molecular Biology Laboratory of INES-Ruhengeri. Type 2 diabetes mellitus (T2DM) cases were defined according to standard diagnostic criteria, including fasting plasma glucose ≥ 126 mg/dL, glycated hemoglobin (HbA1c) ≥ 6.5%, or current use of antidiabetic medication. Non-diabetic controls were individuals without a history of diabetes and with normal fasting blood glucose or HbA1c values where available. The study included 21 participants (12 T2DM cases and 9 controls). Genomic DNA was extracted from peripheral blood samples. Genotyping of the TP53 Arg72Pro polymorphism (rs1042522) was performed using allele-specific polymerase chain reaction (PCR). Fisher’s exact test and odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate associations. T2DM prevalence was higher among females (57.14%) than males (42.86%). The Proline (CCC) allele predominated in both T2DM patients (62.5%) and controls (72.22%), while the Arginine (CGC) allele was less frequent. The heterozygous Arg/Pro genotype was more frequent among T2DM cases (75.0%) than controls (55.6%), although no statistically significant association was identified (p > 0.05). Hardy-Weinberg equilibrium analysis showed no deviation among controls. This preliminary pilot study found no significant association between TP53 Arg72Pro polymorphism and T2DM susceptibility in the studied population. However, its known role in metabolic regulation highlights potential relevance for molecular imaging biomarkers targeting p53-mediated pathways. Further large-scale studies integrating genetic profiling with molecular imaging techniques are warranted.
- Ma, C.X., Ma, X.N., Guan, C.H., Li, Y.D., Mauricio, D. and Fu, S.B. (2022) Cardiovascular Disease in Type 2 Diabetes Mellitus: Progress toward Personalized Management. Cardiovascular Diabetology , 21, Article No. 74. https://doi.org/10.1186/s12933-022-01516-6
- Kung, C.P. and Murphy, M.E. (2016) The Role of the P53 Tumor Suppressor in Metabolism and Diabetes. Journal of Endocrinology , 231, R61-R75. https://doi.org/10.1530/joe-16-0324
- Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., et al . (2009) A Crucial Role for Adipose Tissue P53 in the Regulation of Insulin Resistance. Nature Medicine , 15, 1082-1087. https://doi.org/10.1038/nm.2014
- Madan, E., Gogna, R., Bhatt, M., Pati, U., Kuppusamy, P. and Mahdi, A.A. (2011) Regulation of Glucose Metabolism by P53: Emerging New Roles for the Tumor Suppressor. Oncotarget , 2, 948-957. https://doi.org/10.18632/oncotarget.389
- Li, T., Quan, H., Zhang, H., Lin, L., Lin, L., Ou, Q., et al . (2021) Type 2 Diabetes Is More Predictable in Women than Men by Multiple Anthropometric and Biochemical Measures. Scientific Reports , 11, Article No. 6062. https://doi.org/10.1038/s41598-021-85581-z
- Guo, D., Fang, L., Yu, X., Wang, C., Wang, Y. and Guo, W. (2021) Different Roles of TP53 Codon 72 Polymorphism in Type 2 Diabetes and Its Complications: Evidence from a Case-Control Study on a Chinese Han Population. International Journal of General Medicine , 14, 4259-4268. https://doi.org/10.2147/ijgm.s322840
- Kaňková, K. (2015) Molekulární patofyziologie pozdních komplikací diabetes mellitus-genetická predispozice k rozvoji diabetických komplikací. Vnitřní Lékařství , 61, 438-449.