Abstract
TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor suppressive function requires an activation and stabilization of TP53 in response to cell stressors. However, besides its cancer-preventive functions, TP53 is also known to be involved in diverse cellular processes including metabolism, reproduction, stem cell renewal and development. Indeed, several lines of evidence strongly suggest that TP53 plays crucial role in diabetes. A number of studies have evaluated the association of genetic alterations (single nucleotide variations) in TP53 gene with the development of diabetes. However, the results have not been consistent. The aim of this study was to evaluate whether the C/G polymorphism at codon 72 (Pro72/Arg72), located in exon 4 of TP53, is associated with type 2 diabetes in South Indian population. A total of 74 type 2 diabetic patients and 54 non-diabetic subjects were screened. None of the three genotypes, namely C/C (Pro/Pro), C/G (Pro/Arg), and G/G (Arg/Arg) was found to be significantly associated with type 2 diabetes in our study group. The findings of this study indicate that TP53 codon 72 polymorphism is not associated with increased risk of type 2 diabetes in South Indian population. Further studies with a large cohort size would be necessary to corroborate the observations of this study. Nevertheless, this study represents the first genetic analysis of TP53 variants in South Indian type 2 diabetic patients.
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Abbreviations
- SNP:
-
Single nucleotide polymorphism
- RFLP:
-
Restriction fragment length polymorphism
- BMI:
-
Body mass index
- DM:
-
Diabetes mellitus
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Acknowledgements
The authors are grateful to the patients and the healthy controls who have agreed to take part in this study. The authors thank Nitte (Deemed to be University) for providing resource and infrastructural support. The authors also acknowledge the help of Dr. Neevan D’Souza from KSHEMA in the statistical analysis of the data.
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HKP collected the samples and curated the clinical data. DPN performed the molecular studies and prepared the original draft. BSPD, NB and KK partly performed the experiments and analysed the data. GC participated in discussion and edited the first draft of the manuscript. SMR and HKP conceptualised the study and helped in clinical data compilation. AC supervised the work, analysed the data and edited the draft manuscript.
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Informed consent from the participants were obtained and the study was approved by Ethics Committee of Nitte (Deemed to be University, RefNU/CEC/2018/0).
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11033_2021_6505_MOESM1_ESM.tif
Supplementary file1 Fig. 1 An image showing agarose gel electrophoresis of PCR products of TP53 codon 72. M: 100bp DNA ladder, Lane 1-10: Amplified gene fragment of TP53 codon 72 (TIF 4256 kb)
11033_2021_6505_MOESM2_ESM.tif
Supplementary file2 Fig. 2 A representative image of RFLP analysis at codon 72 of TP53.The RFLP pattern obtained from each sample was compared with the control RFLP pattern to examine the genotype. M-100 base pair ladder; U-undigested PCR product; D-digested PCR product. Sample no. 1 and 5 showed-G/G (wildtype), 2 and 3 - G/C (heterozygous), and 4 - C/C(homozygous) (TIF 4408 kb)
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Punja, H.K., Nanjappa, D.P., Babu, N. et al. TP53 codon 72 polymorphism and type 2 diabetes: a case–control study in South Indian population. Mol Biol Rep 48, 5093–5097 (2021). https://doi.org/10.1007/s11033-021-06505-8
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DOI: https://doi.org/10.1007/s11033-021-06505-8