The bio-inactive MOTS-c variant increases risks of sarcopenia and type 2 diabetes in an age- and physical-activity-dependent manner
(A) A schema of the RNA sequencing analysis in human skeletal muscle from the A allele and C allele carriers of MOTS-c single nucleotide polymorphism (SNP) (m.1382A>C, rs111033358) in 48 Japanese males and females.
(B) Differentially regulated genes in human skeletal muscle between the A and C allele carriers. Age and sex were used as covariates.
(C–D) The overlapped enriched pathways between human skeletal muscles from the A or C allele carriers and skeletal muscles from WT or K14Q MOTS-c-treated immobilized mice. KEGG pathways were used for the enrichment analyses.
(E) Percentage of people with low skeletal muscle mass between the A and C allele carriers of MOTS-c SNP (m.1382A>C, rs111033358) in 1,241 Japanese individuals. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry, and appendicular skeletal muscle mass index (ASMI) was calculated. The cutoff values for low skeletal muscle mass are ASMI <7.0 kg/m2 for men and <5.4 kg/m2 for women.
(F) Odds ratio (OR) and 95% confidence interval of low skeletal muscle mass between the A allele and C allele carriers of MOTS-c SNP (m.1382A>C, rs111033358). OR was adjusted for age and sex.
(G) Skeletal muscle mass assessed by ASMI between the A and C allele carriers of MOTS-c SNP (m.1382A>C, rs111033358) in low and high physical activity groups. A cutoff value for physical activity is 150 min of moderate-to-vigorous physical activity (MVPA) per week base on the World Health Organization guideline. Data are represented as mean ± SEM.
(H) The prevalence of type 2 diabetes in the A and C allele carriers of MOTS-c SNP (m.1382A>C, rs111033358) in 4,966 Japanese males with considering age.
(I) The prevalence of type 2 diabetes in the A and C allele carriers in subjects in the 60s with considering physical activity levels. A cutoff value of the physical activity is 150 min of MVPA per week base on the World Health Organization guideline.
(J) The prevalence of type 2 diabetes in the A and C allele carriers of MOTS-c SNP (m.1382A>C, rs111033358) in 6,890 Japanese females with considering age.∗p < 0.05, ∗∗p < 0.01.