mtDNA Single Nucleotide Variants Associated with Type 2 Diabetes

Enrique García Gaona; Alheli García Gregorio; Camila García Jimenez; Mildred Alejandra López-Olaiz; Paola Mendoza-Ramírez; Daniel Fernandez-Guzman; Rolando Alberto Pillado Sánchez; Axel David Soto Pacheco; Laura Yareni Zuñiga; María Guadalupe Sánchez-Parada; Ana Elizabeth González Santiago; Luis Miguel Román Pintos; Rolando Castañeda Arellano; Luis Daniel Hernández-Ortega; Arieh Roldán Mercado-Sesma; Felipe de Jesús Orozco-Luna; Carlos Villa Angulo; Rafael Villa Angulo; Raúl C. Baptista-Rosas

doi:10.20944/preprints202309.0086.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 30 August 2023 / Approved: 31 August 2023 / Online: 5 September 2023 (10:22:58 CEST)

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1,261 T2D patients and 1,105 control individuals. Our findings revealed significant associations between certain single nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p<0.001), m.14766C>T (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p<0.001), and m.16519T>C (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p=0.012) were significantly associated with diabetes probability. The variant m.16189T>C Previously reported in multiple studies in different populations, it was not found to be associated with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31,; p=0.83). These results provide evidence suggesting a link between some mtDNA polymorphisms and T2D, probably related to association rules and topological patterns and three-dimensional confirmation associated to regions where the changes are, rather than to point mutations in the sequence.

mtDNA; mitogenome; Type 2 diabetes; polymorphism; SNP

Medicine and Pharmacology, Endocrinology and Metabolism

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mtDNA Single Nucleotide Variants Associated with Type 2 Diabetes

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