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Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single-nucleotide polymorphisms in elite master athletes.

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.

SUBMITTER: Crossland H

PROVIDER: S-EPMC7473897 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Sarcopenia is common and contributes to a high risk of mortality among general population. There is no consensus regarding the cut-off values for sarcopenia in terms of mortality among chronic kidney disease patients. This study aimed to explore and validate cut-off points of handgrip strength (HGS) and lean mass index (LMI) for estimating the risk of mortality in peritoneal dialysis (PD) patients. Methods This single-center prospective cohort study enrolled 1089 incident PD patients between October 2002 and July 2019. All patients were followed until death, transfer to hemodialysis, receiving renal transplantation or the end date of study (December 2019). All participants were randomly sampled to development cohort (70% participants) and validation cohort (30% participants), matched by gender and diabetes. Lean body mass was calculated by using the equation published by our center. Cubic spline regression analysis was used to examine the relationship between HGS or LMI values and mortality, and explore the cut-off points after adjusting for age, diabetes, cardiovascular disease and serum albumin in the development cohort. The derived cut-off values were verified by the agreement rate for predicting mortality and then compared with cut-off values from various clinical guidelines in the validation cohort. Results All 1089 patients were followed up with the median of 36.0 (18.0, 71.0) months. In the development cohort, cut-off points for predicting the higher mortality were derived as 24.5 kg and 14 kg of HGS for males and females, 16.7 kg/m2 and 13.8 kg/m2 of LMI for males and females respectively. In the validation cohort, these cut-off values significantly predicted worse outcomes, with HR 1.96 (1.35, 2.84) of HGS and HR 1.76 (1.26, 2.47) of LMI for all-cause mortality after multivariate adjustment. The newly derived cut-off points of HGS have numerically higher prognostic values in all-cause mortality compared with those from current clinical guidelines, and agreement rates of HGS were 65.2 versus 62.5–64.6 respectively. Conclusions The derived cut-off values of HGS and LMI have sufficient and better prognostic value in predicting all-cause mortality in PD patients compared with the cut-off values in the existing guidelines. These cut-off values are only validated in a single population, thus limiting the generalizability.

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Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single-nucleotide polymorphisms in elite master athletes.

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