Impact of the peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1beta expression and fibre type composition in human skeletal muscle

Diabetologia. 2007 Aug;50(8):1615-20. doi: 10.1007/s00125-007-0729-6. Epub 2007 Jun 20.


Aims/hypothesis: Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta, also known as PPARGC1B) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1beta expression, in vivo metabolism and markers for muscle fibre type composition.

Materials and methods: The PGC-1beta Ala203Pro polymorphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1beta expression, in vivo metabolism and markers for fibre type composition.

Results: Insulin-stimulated non-oxidative glucose metabolism (NOGM; p = 0.025) and glycolytic flux rate (GF; p = 0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p < or = 0.001), there was no significant age-related decline in PGC-1beta expression in carriers of the 203Pro allele (p > or = 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1beta expression. Finally, PGC-1beta expression correlated positively with markers for oxidative fibres in human muscle.

Conclusions/interpretation: This study suggests that young carriers of a PGC-1beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1beta expression in muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Carrier Proteins / genetics*
  • Gene Expression
  • Gene Frequency
  • Genotype
  • Glucose / metabolism
  • Humans
  • Middle Aged
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle, Skeletal / metabolism*
  • Polymorphism, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • Twins / genetics


  • Carrier Proteins
  • PPARGC1B protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Glucose