Deficiency of Peptidylglycine-alpha-amidating Monooxygenase, a Cause of Sarcopenic Diabetes Mellitus
Authors' conclusion
PAM-AMA genetic deficiency results in a prediabetic sarcopenic phenotype. Early identification of PAM LoF carriers would allow targeted exercise interventions and calls for novel therapies that restore enzymatic activity.
Study context
- Population
- Participants of the Malmö Diet and Cancer (MDC-Cardiovascular cohort), Malmö Preventive Project and UK Biobank
- Exposure
- Carriers of PAM loss-of-function variants vs non-carriers
- Outcome
- Endocrine-metabolic traits suggested by prior literature, muscle mass, muscle function and sarcopenia
Methodological detailsexome-wide association analysis, cohort studies (Malmö Diet and Cancer (MDC), Malmö Preventive Project (MPP), UK Biobank (UKB))
- Exome-wide association analysis
- Cohort studies (MDC, MPP, UKB)
Main finding
As reported in the abstract
Ser539Trp (minor allele frequency 0.7%): decrease in PAM-amidating activity (PAM-AMA), SD units
2.33
95% CI 2.52/2.15P = 2.5E-140
Asp563Gly (minor allele frequency 5%): decrease in PAM-AMA, SD units (1.04/0.92; P = 1.12E-225)
0.98
Ser539Trp: sarcopenia, OR (95% CI 1.16/1.47; P = 9.8E-06), independent of age and diabetes
1.31
Observational data: associations, not effects.
Original publication
Deficiency of Peptidylglycine-alpha-amidating Monooxygenase, a Cause of Sarcopenic Diabetes Mellitus. J Clin Endocrinol Metab. Published 13 August 2024. doi:10.
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