Mitochondrial Haplogroup N9a Confers Resistance against Type 2 Diabetes in Asians

Abstract

Because mitochondria play pivotal roles in both insulin secretion from the pancreatic beta cells and insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type 2 diabetes mellitus (T2DM). The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with T2DM and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with T2DM and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups (i.e., F, B, A, N9a, M7a, M7b, G, D4a, D4b, and D5). Multivariate logistic-regression analysis with adjustment for age and sex revealed that the mitochondrial haplogroup N9a was significantly associated with resistance against T2DM (P=.0002) with an odds ratio of 0.55 (95% confidence interval 0.40-0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplogroup might confer resistance against T2DM.

Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents

“…The association with haplogroup J was supported by a study in a white Brazilian population, which also found an association with haplogroup T [19]. More recently, there has been a report that haplogroup N9a confers resistance to type 2 diabetes in Asians [20]. In the largest association study to date [21], an association between both diabetes disease status and related metabolic traits and common European mitochondrial variants was tested for in several populations of European origin.…”

The mitochondrial‐derived peptide MOTS‐c: a player in exceptional longevity?

“…reporting no association between mtDNA haplogroups and EL (Pinos et al ., 2012) but Dominguez‐Garrido and co‐workers finding that the Caucasian haplogroup J (which would be associated with lower mtDNA damage) might confer a higher chance to attain high longevity (85+years) compared with other haplogroups in Northern Spaniards (Domínguez‐Garrido et al ., 2009). On the other hand, although mtDNA haplogroups D4b2b, D4a, and D5 are not associated with type 2 diabetes (Fuku et al ., 2007), they are linked with EL in Japanese population (Alexe et al ., 2007; Bilal et al ., 2008). We also showed that the mtDNA m.1382A>C polymorphism, which is specific for the ancestor haplogroup D4b2, is associated with EL in the Japanese population (Alexe et al ., 2007).…”

Extensive and rapid screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss

“…shtml) and recent reports. [16][17][18][19] Consequently, it is also necessary to distinguish pathogenic mtDNA mutations from mtSNPs.…”