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

• Published in: Journal of diabetes investigation Vol. 13; no. 1; pp. 201 - 208
• Main Authors: Shen, Feng‐Chih, Weng, Shao‐Wen, Tsai, Meng‐Han, Su, Yu‐Jih, Li, Sung‐Chou, Chang, Shun‐Jen, Chen, Jung‐Fu, Chang, Yen‐Hsiang, Liou, Chia‐Wei, Lin, Tsu‐Kung, Chuang, Jiin‐Haur, Lin, Ching‐Yi, Wang, Pei‐Wen
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.01.2022; John Wiley and Sons Inc; Wiley
• Subjects: Alleles; Asian People - genetics; Body mass index; Cholesterol; Creatinine; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; DNA, Mitochondrial - genetics; Female; Genetic diversity; Genetic Predisposition to Disease - genetics; Genomes; Glucose; Haplotypes; Haplotypes - genetics; Health risk assessment; High-Throughput Nucleotide Sequencing; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - therapeutic use; Insulin resistance; Insulin Resistance - genetics; Male; Metabolic disorders; Middle Aged; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mutation; Next-generation sequencing; Original; Polymorphism, Single Nucleotide; Single-nucleotide polymorphism; Taiwan - ethnology; Taiwan; Minneapolis Minnesota; United States > US; Insulin; Mitochondria; Diabetes
• ISSN: 2040-1116; 2040-1124; 2040-1124
• DOI: 10.1111/jdi.13629

ABSTRACT 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. Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement in patients with T2DM.