Source:http://linkedlifedata.com/resource/pubmed/id/21063444
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2011-1-13
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| pubmed:abstractText |
Muscle strength is important in functional activities of daily living and the prevention of common pathologies. We describe the two-staged fine mapping of a previously identified linkage peak for knee strength on chr12q12-14. First, 209 tagSNPs in/around 74 prioritized genes were genotyped in 500 Caucasian brothers from the Leuven Genes for Muscular Strength study (LGfMS). Combined linkage and family-based association analyses identified activin receptor 1B (ACVR1B) and inhibin ? C (INHBC), part of the transforming growth factor ? pathway regulating myostatin - a negative regulator of muscle mass - signaling, for follow-up. Second, 33 SNPs, selected in these genes based on their likelihood to functionally affect gene expression/function, were genotyped in an extended sample of 536 LGfMS siblings. Strong associations between ACVR1B genotypes and knee muscle strength (P-values up to 0.00002) were present. Of particular interest was the association with rs2854464, located in a putative miR-24-binding site, as miR-24 was implicated in the inhibition of skeletal muscle differentiation. Rs2854464 AA individuals were ?2% stronger than G-allele carriers. The strength increasing effect of the A-allele was also observed in an independent replication sample (n=266) selected from the Baltimore Longitudinal Study of Aging and a Flemish Policy Research Centre Sport, Physical Activity and Health study. However, no genotype-related difference in ACVR1B mRNA expression in quadriceps muscle was observed. In conclusion, we applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1476-5438
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| pubmed:author |
pubmed-author:AerssensJeroenJ,
pubmed-author:BeunenGaston PGP,
pubmed-author:De MarsGuntherG,
pubmed-author:DelecluseChristopheC,
pubmed-author:FerrucciLuigiL,
pubmed-author:HuygensWimW,
pubmed-author:LambrechtsDietherD,
pubmed-author:MetterE JeffreyEJ,
pubmed-author:PeetersMaarten WMW,
pubmed-author:RothStephen MSM,
pubmed-author:ThomisMartine AMA,
pubmed-author:VincentBarbaraB,
pubmed-author:VlietinckRobertR,
pubmed-author:WijmengaCiscaC,
pubmed-author:WindelinckxAnA
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| pubmed:issnType |
Electronic
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
208-15
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| pubmed:meshHeading |
pubmed-meshheading:21063444-Activin Receptors, Type I,
pubmed-meshheading:21063444-Adolescent,
pubmed-meshheading:21063444-Adult,
pubmed-meshheading:21063444-Chromosome Mapping,
pubmed-meshheading:21063444-Chromosomes, Human, Pair 12,
pubmed-meshheading:21063444-European Continental Ancestry Group,
pubmed-meshheading:21063444-Genetic Linkage,
pubmed-meshheading:21063444-Genome-Wide Association Study,
pubmed-meshheading:21063444-Genotype,
pubmed-meshheading:21063444-Humans,
pubmed-meshheading:21063444-Knee,
pubmed-meshheading:21063444-Male,
pubmed-meshheading:21063444-Muscle, Skeletal,
pubmed-meshheading:21063444-Muscle Strength,
pubmed-meshheading:21063444-Myostatin,
pubmed-meshheading:21063444-Phenotype,
pubmed-meshheading:21063444-Polymorphism, Single Nucleotide,
pubmed-meshheading:21063444-Siblings,
pubmed-meshheading:21063444-Transforming Growth Factor beta,
pubmed-meshheading:21063444-Young Adult
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| pubmed:year |
2011
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| pubmed:articleTitle |
Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene.
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| pubmed:affiliation |
Research Center for Exercise and Health, Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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