Abstract
Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single-nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS in a population of elite master athletes (MA) and age-matched controls as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals [consisting of 48 MA (71 ± 6 yr, age-graded performance 83 ± 9%) and 48 older controls (75 ± 6 yr)]. SNP validation and sample genotyping were conducted using the tetra-primer amplification refractory mutation system (ARMS). For the three SNPs analyzed that were previously associated with LBM (FTO, IRS1, and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P < 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P < 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P < 0.05, Fisher's exact test). Collectively, of the six SNPs analyzed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition and of TGFA in strength may highlight a genetic component of the elite MA phenotype.
Highlights
Lean body mass (LBM) plays an important role in metabolic function, mobility and healthy ageing, where progressive declines in LBM and concurrent increases in lipid infiltration can have detrimental impacts related to functional impairments and disability [13, 14, 18, 37].declines in muscle strength with ageing are associated with impaired quality-of-life in older adults and increased risk of frailty and hospitalizations [2, 34]
In relation to single nucleotide polymorphisms (SNPs) that were previously associated with LBM, multinomial logistic regression showed no significant association of total lean mass, % LBM or appendicular lean mass with insulin receptor substrate 1 (IRS1; rs2943656; effect allele A), FTO or A
For ADAMTSL3 there was a significant association with % LBM, where the TT genotype was associated with higher %
Summary
Declines in muscle strength with ageing are associated with impaired quality-of-life in older adults and increased risk of frailty and hospitalizations [2, 34]. Handgrip strength (HGS) is a widely used marker of frailty, and a strong predictor of morbidities and survival [21, 38]. A recent study identified and replicated a set of five loci for total lean body mass [42]. Three of these SNPs (near/in genes for IRS1, ADAMTSL3 and VCAN) were successfully replicated for appendicular lean mass.
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