Mitochondrial haplogroups have a better correlation to insulin requirement than nuclear genetic variants for type 2 diabetes mellitus in Taiwanese individuals

Aims/Introduction Identifying diabetes-susceptible genetic variants will help to provide personalized therapy for the management of type 2 diabetes. Previous studies have reported a genetic risk score (GRS), computed by the sum of nuclear DNA (nDNA) risk alleles, that may predict the future requirement for insulin therapy. Although mitochondrial dysfunction has a close association with insulin resistance (IR), there are few studies investigating whether genetic variants of mitochondrial DNA (mtDNA) will affect the clinical characteristics of type 2 diabetes. Materials and Methods Mitochondrial haplogroups were determined using mtDNA whole genome next generation sequencing and 13 single nucleotide polymorphisms (SNPs) in nDNA susceptibility loci of 13 genes in 604 Taiwanese subjects with type 2 diabetes. A GRS of nDNA was computed by summation of the number of risk alleles. The correlation between the mtDNA haplogroup and the clinical characteristics of type 2 diabetes was assessed by logistic regression analysis. The results were compared with the GRS subgroups for the risk of insulin requirement. Results Mitochondrial haplogroups modulate the clinical characteristics of type 2 diabetes, in which patients harboring haplogroup D4, compared with those harboring non-D4 haplotypes, were less prone to require insulin treatment, after adjusting for age, gender, and diabetes duration. However, there was no association between insulin requirement and GRS calculated from nuclear genetic variants. Conclusions Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement. The results highlight the role of mitochondria in the management of common metabolic diseases.

Automated summary

Mitochondrial haplogroups have a significant impact on the clinical characteristics of type 2 diabetes, with patients carrying the D4 haplogroup being less likely to require insulin treatment compared to those with non-D4 haplotypes. However, there is no significant association between insulin requirement and genetic variants in nuclear DNA. This highlights the role of mitochondria in the management of common metabolic diseases.