ABSTRACT
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 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association 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 specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.
ABSTRACT
Type 2 diabetes (T2D) has been linked to the expression of Human Leukocyte Antigens, principally to the Major Histocompatibility Complex Class II, with only scarce reports of Major Histocompatibility Complex Class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC Class I related to T2D in the Mexican population using the Genome-Wide Association Studies Slim Initiative in Genomic Medicine of the Americas (GWAS SIGMA) database. This database contains information on 3848 Mexican individuals with T2D and 4366 control individuals from the same population without a clinical or hereditary history of the disease. The searching criteria considered a p-value of <0.005 and an odds ratio (OR) of >1.0. Ten novel, statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01) and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related to the development of T2D complications.
