scholarly journals Disentangling the Genetics of Sarcopenia: prioritization of NUDT3 and KLF5 as genes for lean mass and HLA-DQB1-AS1 for hand grip strength based on associated SNPs

2019 ◽  
Author(s):  
Abhishek N. Singh
Keyword(s):  
Grip Strength ◽  
Muscle Mass ◽  
Lean Mass ◽  
Musculoskeletal Diseases ◽  
Hand Grip Strength ◽  
Muscle Disease ◽  
P Value ◽  
Hand Grip ◽  
Increased Risk ◽  
Regulatory Snps

Abstract Background: Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because may allows us to identify new genetic markers or identify patients with an increased risk to develop a specific musculoskeletal diseases or condition such as sarcopenia. It might also allow us to identify drugs that affect muscle in ways unknown before and therefore to reposition drugs to other uses, in accordance to their newly found target. We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean muscle mass, which can then be a target for downstream lab experimentation validation. SNPs associated with various disease traits for the muscles and specific loci were chosen according to their muscle phenotype association p-value, as traditionally done in the GWASs. We developed and applied a combination of expression quantitative trait loci study (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle). Results: We found NUDT3 and KLF5 for lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. Conclusion: TWAS approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, here, Sarcopenia. Potentially regulatory SNPs associated with these genes can be analyzed with respect to TADs and then targeted for knock out in either C2C12 mouse myoblast cells, adipocytes or any other relevant cell, depending on the phenotype it is hypothesized to affect, as a downstream experimental validation plan.

scholarly journals Disentangling the Genetics of Sarcopenia: prioritization of NUDT3 and KLF5 as genes for lean mass and HLA-DQB1-AS1 for hand grip strength based on associated SNPs

2020 ◽  
Author(s):  
Abhishek N. Singh ◽  
Bili Gasman
Keyword(s):  
Grip Strength ◽  
Lean Mass ◽  
Association Studies ◽  
Hand Grip Strength ◽  
Muscle Disease ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Hand Grip ◽  
Increased Risk ◽  
Regulatory Snps

Abstract Background: Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because it may allow to identify patients with an increased risk to develop a specific musculoskeletal disease or condition such as sarcopenia based on genetic markers. We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean mass, which can then be a target for downstream lab experimentation validation. Single nuclear polymorphisms (SNPs) associated with various disease traits of muscles and specific genes were chosen according to their muscle phenotype association p-value, as traditionally done in Genome Wide Association Studies, GWAS. We've developed and applied a combination of expression quantitative trait loci (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle). Results: We found NUDT3 and KLF5 for lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. Conclusion: Transcriptome Wide Association Studies, TWAS, approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, in this case, Sarcopenia. Potentially regulatory SNPs associated with these genes can be then wet-lab verified, depending on the phenotype it is hypothesized to affect.

scholarly journals Disentangling the Genetics of Sarcopenia: prioritization of NUDT3 and KLF5 as genes for lean mass and HLA-DQB1-AS1 for hand grip strength based on associated SNPs

2020 ◽  
Author(s):  
Abhishek N. Singh ◽  
Bili Gasman
Keyword(s):  
Grip Strength ◽  
Lean Mass ◽  
Association Studies ◽  
Hand Grip Strength ◽  
Muscle Disease ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Hand Grip ◽  
Increased Risk ◽  
Regulatory Snps

Abstract Background: Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because it may allow to identify patients with an increased risk to develop a specific musculoskeletal disease or condition such as sarcopenia based on genetic markers. We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean mass, which can then be a target for downstream lab experimentation validation. Single nuclear polymorphisms (SNPs) associated with various disease traits of muscles and specific genes were chosen according to their muscle phenotype association p-value, as traditionally done in Genome Wide Association Studies, GWAS. We've developed and applied a combination of expression quantitative trait loci (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle). Results: We found NUDT3 and KLF5 for lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. Conclusion: Transcriptome Wide Association Studies, TWAS, approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, in this case, Sarcopenia. Potentially regulatory SNPs associated with these genes can be then wet-lab verified, depending on the phenotype it is hypothesized to affect.

scholarly journals Lower Percentage of Fat Mass among Tai Chi Chuan Practitioners

2020 ◽  
Vol 17 (4) ◽  
pp. 1232
Author(s):  
Silvia Stagi ◽  
Azzurra Doneddu ◽  
Gabriele Mulliri ◽  
Giovanna Ghiani ◽  
Valeria Succa ◽  
...  
Keyword(s):  
Body Composition ◽  
Grip Strength ◽  
Muscle Mass ◽  
Fat Mass ◽  
Tai Chi ◽  
Hand Grip Strength ◽  
Middle Aged ◽  
Tai Chi Chuan ◽  
Hand Grip ◽  
Total Body

The aim of the study was to analyze total and regional body composition in Tai Chi Chuan (TCC) middle-aged and elderly practitioners. A cross-sectional study on 139 Italian subjects was realized: 34 TCC practitioners (14 men, 20 women; 62.8 ± 7.4 years) and 105 sedentary volunteers (49 men, 56 women; 62.8 ± 6.4 years). Anthropometric measurements (height, weight, arm, waist, and calf circumferences), hand-grip strength, and physical capacity values were collected. Total and regional (arm, leg, and trunk) body composition was analyzed by means of specific bioelectrical impedance vector analysis (specific BIVA). TCC practitioners of both sexes were characterized by a normal nutritional status, normal levels of physical capacity, and normal values of hand-grip strength. Compared to controls, they showed lower percentages of fat mass (lower specific resistance) in the total body, the arm, and the trunk, and higher muscle mass (higher phase angle) in the trunk, but lower muscle mass in the arm. Sexual dimorphism was characterized by higher muscle mass (total body, arm, and trunk) and lower %FM (arm) in men; sex differences were less accentuated among TCC practitioners than in the control. TCC middle-aged and elderly practitioners appear to be less affected by the process of physiological aging and the associated fat mass changes, compared to sedentary people.

scholarly journals Impact of daily protein and energy intake and distribution on muscle mass and strength in Danish older individuals-The CALM study

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yusuke Nishimura ◽  
Grith Hojfeldt ◽  
Simon Rønnow Schacht ◽  
Kenneth Mertz ◽  
Morten Hjulmand ◽  
...  
Keyword(s):  
Total Energy ◽  
Grip Strength ◽  
Muscle Mass ◽  
Energy Intake ◽  
Protein Intake ◽  
Knee Extension ◽  
Hand Grip Strength ◽  
Energy Ratio ◽  
Older Individuals ◽  
Hand Grip

AbstractThe importance of dietary protein for the maintenance of muscle mass and strength is heavily discussed. However, adequate energy intake is an underlying assumption but often not considered. In this study, we investigated the impact of daily intake and meal distribution of both protein and energy on muscle mass and strength. In a cross-sectional study, a total of 184 older individuals (gender: 86F/98M, age: 70.2 ± 3.9 yrs, BMI: 25.4 ± 3.7 kg/m2; means ± SD) were recruited. Participants underwent a 3-day weighed dietary record, Dual-energy X-ray Absorptiometry (DXA) scan, hand-grip strength, and Maximal Voluntary Isometric knee-extension Contraction (MVIC). Participants were divided into two categories: lower (LOW; < 0.83 g/adjusted(a)BW/day) or higher (HIGH; ≥ 1.1 g/aBW/day) protein intake levels analysed by gender to characterize a daily protein and energy intake pattern. Main meal protein and energy intake distributions were calculated, and correlations were made. Further, energy intake at breakfast and lunch divided by total energy intake (energy ratio) was correlated with appendicular skeletal muscle index (ASMI), hand-grip strength, and MVIC were determined using the LOW/HIGH-protein-intake categorization. Further, gender-specific ASMI, hand-grip strength and knee extension were compared based on the following four distinct daily protein intake ranges: < 0.66; ≥ 0.66- < 0.83; ≥ 0.83- < 1.1; ≥ 1.1 g/aBW/day. A positive correlation appeared between protein and energy intake in all main meals (r ≥ 0.57, p < 0.0001). In the LOW category, positive correlations were found between energy ratio and ASMI (r = 0.16, p = 0.048), hand-grip strength (r = 0.40, p = 0.0009), and MVIC (r = 0.36, p = 0.0019), whereas no associations were found in the HIGH category. ASMI, hand grip, and MVIC were similar regardless of the protein intake ranges, though with women being lower than men (p < 0.05) in all outcomes. These results show that total daily protein intake did not affect muscle mass and strength in our cohort. However, our data demonstrate that greater energy intake in breakfast and lunch relative to total energy intake is associated with higher muscle mass and strength, particularly when protein intake is lower than 0.83 g/aBW/day, indicating the potential importance of meal energy content at lower intakes of protein.

scholarly journals Cross-sectional associations among P3NP, HtrA, Hsp70, Apelin and sarcopenia in Taiwanese population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuan-Yuei Chen ◽  
Yi-Lin Chiu ◽  
Tung-Wei Kao ◽  
Tao-Chun Peng ◽  
Hui-Fang Yang ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Mrna Expression ◽  
Grip Strength ◽  
Muscle Mass ◽  
Hand Grip Strength ◽  
Community Dwelling ◽  
Cutoff Point ◽  
Walking Distance ◽  
Skeletal Mass ◽  
Hand Grip

Abstract Background Sarcopenia is a multifactorial pathophysiologic condition of skeletal muscle mass and muscle strength associated with aging. However, biomarkers for predicting the occurrence of sarcopenia are rarely discussed in recent studies. The aim of the study was to elucidate the relationship between sarcopenia and several pertinent biomarkers. Methods Using the Gene Expression Omnibus (GEO) profiles of the National Center for Biotechnology Information, the associations between mRNA expression of biomarkers and sarcopenia were explored, including high temperature requirement serine protease A1 (HtrA1), procollagen type III N-terminal peptide (P3NP), apelin, and heat shock proteins 70 (Hsp72). We enrolled 408 community-dwelling adults aged 65 years and older with sarcopenia and nonsarcopenia based on the algorithm proposed by the Asian Working Group for Sarcopenia (AWGS). Muscle strength is identified by hand grip strength using an analogue isometric dynamometer. Muscle mass is estimated by skeletal mass index (SMI) using a bioelectrical impedance analysis. Physical performance is measured by gait speed using 6 m walking distance. The associations between these biomarkers and sarcopenia were determined using receiver operating characteristic (ROC) curve analysis and multivariate regression models. Results From the GEO profiles, the sarcopenia gene set variation analysis score was correlated significantly with the mRNA expression of APLNR (p < 0.001) and HSPA2 (p < 0.001). In our study, apelin was significantly associated with decreased hand grip strength with β values of − 0.137 (95%CI: − 0.229, − 0.046) in men. P3NP and HtrA1 were significantly associated with increased SMI with β values of 0.081 (95%CI: 0.010, 0.153) and 0.005 (95%CI: 0.001, 0.009) in men, respectively. Apelin and HtrA1 were inversely associated with the presence of sarcopenia with an OR of 0.543 (95%CI: 0.397–0.743) and 0.003 (95%CI: 0.001–0.890) after full adjustment. The cutoff point of HtrA1 was associated with the presence of sarcopenia with an OR of 0.254 (95%CI: 0.083–0.778) in men. The cutoff point of apelin was negatively associated with the presence of sarcopenia with an OR of 0.254 (95%CI: 0.083–0.778). Conclusion Our study highlights that P3NP, HtrA, and apelin are useful for diagnosis of sarcopenia in the clinical setting.

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