A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c — VialBase Research
m.1382A>C polymorphism causes K14Q substitution in MOTS-c peptide
- m.1382A>C polymorphism causes K14Q substitution in MOTS-c peptide
- This variant is associated with increased risk of type 2 diabetes in men
- The same variant is associated with exceptional longevity in Japanese populations
- Suggests MOTS-c polymorphisms modulate metabolic aging trajectory
- Links mitochondrial genetic variation to metabolic disease risk
Summary
Genetic association study investigating the m.1382A>C polymorphism in the mitochondrial gene encoding MOTS-c. This variant produces a K14Q amino acid substitution in the MOTS-c peptide (lysine to glutamine at position 14). The study found this variant is associated with increased type 2 diabetes risk in men, while paradoxically also being associated with exceptional longevity in Japanese populations.
Key Findings
- The m.1382A>C variant (K14Q) alters the MOTS-c peptide at a functionally important position
- Associated with increased type 2 diabetes risk in men — pro-diabetogenic effect
- Paradoxically associated with exceptional longevity in Japanese populations
- Suggests the same genetic variant may have context-dependent effects on metabolic aging
- Provides human genetic evidence that MOTS-c function directly impacts metabolic disease
Relevance to MOTS-c
Critical human genetic evidence linking MOTS-c to real metabolic outcomes. The K14Q variant demonstrates that even single amino acid changes in MOTS-c alter metabolic disease risk, validating the peptide’s functional importance. The paradoxical longevity association suggests complex pleiotropic effects. This study supports the therapeutic rationale for MOTS-c supplementation — if genetic deficiency increases disease risk, exogenous supplementation may be protective.
Citation
Zempo H, et al. Aging (Albany NY). 2019;11(21):9527-9543. PMID: 31607007
See Also
- Parent compound: MOTS-c