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Published on: July 15, 2014
TNF promoter polymorphisms associated with muscle phenotypes in humans
Dongmei Liu1, E Jeffrey Metter, Luigi Ferrucci
1Dept. of Kinesiology, Univ. of Maryland, College Park, MD 20742-2611, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 19, 2008
Summary
Genetic variations in the Tumor Necrosis Factor-alpha (TNF-alpha) gene promoter are linked to reduced muscle mass in men. Specific TNF gene single-nucleotide polymorphisms (SNPs) correlate with lower muscle mass and strength, suggesting a genetic influence on muscle phenotypes.
Area of Science:
- Genetics
- Muscle Physiology
- Molecular Biology
Background:
- Tumor Necrosis Factor-alpha (TNF-alpha) is a key catabolic factor impacting skeletal muscle.
- Interindividual differences in TNF-alpha production are influenced by single-nucleotide polymorphisms (SNPs) in the TNF gene promoter.
- These SNPs regulate TNF-alpha gene transcription.
Purpose of the Study:
- To investigate the association between specific TNF promoter SNPs and muscle phenotypes.
- To explore the potential biological significance of these genetic variations on muscle mass and strength.
- To determine if genetic variation in the TNF locus contributes to variations in muscle phenotypes in humans.
Main Methods:
- Genotyping of 1,050 volunteers from the Baltimore Longitudinal Study of Aging (BLSA).
- Analysis of five TNF promoter single-nucleotide polymorphisms (SNPs).
- Measurement of regional and total body muscle mass, and muscle strength (arm and leg).
Main Results:
- High-expression alleles at TNF promoter positions -1031 and -863 were associated with lower muscle mass in men.
- Carriers of the -1031C allele showed reduced arm muscle mass and appendicular skeletal muscle mass (ASM).
- A specific haplotype (1031C-863A-857C-308G-238G) was linked to significantly lower arm, trunk, and ASM in men.
Conclusions:
- Genetic variations within the TNF gene locus are associated with interindividual differences in muscle phenotypes, particularly in men.
- Specific TNF promoter SNPs and haplotypes may influence skeletal muscle mass and potentially strength.
- These findings highlight the role of genetic factors in modulating muscle health and susceptibility to muscle loss.
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