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Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans.

ABSTRACT: Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19-90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2+/-1.9 vs. 118.6+/-4.1 N.m, 30 degrees/s, respectively, P=0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat-free mass than noncarriers (16.6+/-0.3 vs. 17.5+/-0.2 kg, respectively, P=0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships.

SUBMITTER: Walsh S

PROVIDER: S-EPMC2646094 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans.

Walsh Sean S Metter E Jeffrey EJ Ferrucci Luigi L Roth Stephen M SM

Journal of applied physiology (Bethesda, Md. : 1985) 20070308 6

Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify association ...[more]

PMID: 17347381

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Project description:Increasing age is accompanied by many changes, including declining functional skeletal muscle health and immune dysfunction. Peripheral blood mononuclear cells (PBMCs) are circulating cells that assemble an immune response, but their whole genome transcriptome has not been studied in the context of age-related muscle health. Consequently, this article explored associations between three muscle variables indicative of functional muscle health - maximum handgrip strength (muscle strength), appendicular skeletal muscle mass index (ASMI, muscle mass), and gait speed (physical performance) - and two groups of bioinformatics-generated PBMC gene expression features (gene expression-estimated leukocyte subset proportions and gene clusters). We analyzed cross-sectional data from 95 home-dwelling healthy women ≥ 70 years, using "cell-type identification by estimating relative subsets of RNA transcripts" (CIBERSORT) to estimate leukocyte subset proportions and "weighted correlation network analysis" (WGCNA) to generate gene clusters. Associations were studied using linear regression models and relevant gene clusters were subjected to gene set enrichment analysis using gene ontology. Gait speed and ASMI associated with CIBERSORT-estimated monocyte proportions (β = - 0.090, 95% CI = (- 0.146, - 0.034), p-value = 0.002 for gait speed, and β = - 0.206, 95% CI = (- 0.385, - 0.028), p-value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions (β = - 0.026, 95% CI = (- 0.043, - 0.008), p-value = 0.004). Furthermore, maximum handgrip strength associated with nine WGCNA gene clusters, enriched in processes related to immune function and skeletal muscle cells (β in the range - 0.007 to 0.008, p-values < 0.05). These results illustrate interactions between skeletal muscle and the immune system, supporting the notion that age-related functional muscle health and the immune system are closely linked.

Dataset Information

Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans.

Publications

Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans.

Similar Datasets

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