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Myostatin related gene associations ...

Walsh, Sean.

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Myostatin related gene associations with muscle mass and strength in humans.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Myostatin related gene associations with muscle mass and strength in humans./
Author:	Walsh, Sean.
Description:	105 p.
Notes:	Adviser: Stephen M. Roth.
Contained By:	Dissertation Abstracts International67-06B.
Subject:	Biology, Animal Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3222367
ISBN:	9780542732317

Myostatin related gene associations with muscle mass and strength in humans.
Walsh, Sean.

Myostatin related gene associations with muscle mass and strength in humans. - 105 p.

Adviser: Stephen M. Roth.

Thesis (Ph.D.)--University of Maryland, College Park, 2006.

Introduction. The gradual decline in muscle mass with age is known as sarcopenia, and has been associated with an increased risk of falls, hip fractures, and functional decline. However, there is large inter-individual variability in this decline, even among people of a similar age and sex. Heritability studies have shown that genetic factors can account for up to 90% of this variation in muscle mass and &sim;65% in muscle strength. Myostatin is a negative regulator of skeletal muscle and plays a key role in muscle development and the maintenance of muscle mass. However, DNA sequence variation within this gene has not been consistently associated with skeletal muscle mass nor muscle strength in humans. Purpose. The purpose of this dissertation was to examine genetic variation in follistatin and Activin RIIB (ACVR2B), two myostatin related genes, to explore associations with skeletal muscle related phenotypes. Methods. Three hundred fifteen Caucasian males and 278 Caucasian females aged 19-90 years from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings. Whole-body soft tissue composition was measured by dual-energy X-ray absorptiometry. Peak torque (strength) was measured using an isokinetic dynamometer. Results. Women heterozygous for ACVR2B haplotype groups 1 and 2 exhibited significantly less concentric quadriceps muscle strength than women homozygous for haplotype group 2 (108.7 +/- 2.2 vs. 118.6 +/- 4.1 N·m, .52rad/sec, respectively, p <0.05). No significant association was observed in men. However, men homozygous for follistatin haplotype group 1 exhibited significantly greater total leg FFM than men heterozygous for follistatin haplotype groups 1 and 3 (17.8 +/- 0.2 vs. 16.7 +/- 0.4 kg, respectively, p <0.05) and significantly greater total leg FFM than non-carriers of follistatin haplotype group 1 (17.8 +/- 0.2 vs. 16.5 +/- 0.5 kg, respectively, p <0.05). Moreover, male carriers of follistatin haplotype group 3 exhibited significantly less total leg FFM than non-carriers (16.6 +/- 0.3 vs. 17.5 +/- 0.2 kg, respectively, p <0.05). No significant associations between these groups were observed in women. Conclusions. The data indicate that the ACVR2B and follistatin loci may contribute to the inter-individual variation in skeletal muscle mass and strength.

ISBN: 9780542732317Subjects--Topical Terms:

1017835
Biology, Animal Physiology.

Myostatin related gene associations with muscle mass and strength in humans.
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035 $a (UMI)AAI3222367
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100 1 $a Walsh, Sean. $3 1293213
245 1 0 $a Myostatin related gene associations with muscle mass and strength in humans.
300 $a 105 p.
500 $a Adviser: Stephen M. Roth.
500 $a Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 2947.
502 $a Thesis (Ph.D.)--University of Maryland, College Park, 2006.
520 $a Introduction. The gradual decline in muscle mass with age is known as sarcopenia, and has been associated with an increased risk of falls, hip fractures, and functional decline. However, there is large inter-individual variability in this decline, even among people of a similar age and sex. Heritability studies have shown that genetic factors can account for up to 90% of this variation in muscle mass and &sim;65% in muscle strength. Myostatin is a negative regulator of skeletal muscle and plays a key role in muscle development and the maintenance of muscle mass. However, DNA sequence variation within this gene has not been consistently associated with skeletal muscle mass nor muscle strength in humans. Purpose. The purpose of this dissertation was to examine genetic variation in follistatin and Activin RIIB (ACVR2B), two myostatin related genes, to explore associations with skeletal muscle related phenotypes. Methods. Three hundred fifteen Caucasian males and 278 Caucasian females aged 19-90 years from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings. Whole-body soft tissue composition was measured by dual-energy X-ray absorptiometry. Peak torque (strength) was measured using an isokinetic dynamometer. Results. Women heterozygous for ACVR2B haplotype groups 1 and 2 exhibited significantly less concentric quadriceps muscle strength than women homozygous for haplotype group 2 (108.7 +/- 2.2 vs. 118.6 +/- 4.1 N·m, .52rad/sec, respectively, p <0.05). No significant association was observed in men. However, men homozygous for follistatin haplotype group 1 exhibited significantly greater total leg FFM than men heterozygous for follistatin haplotype groups 1 and 3 (17.8 +/- 0.2 vs. 16.7 +/- 0.4 kg, respectively, p <0.05) and significantly greater total leg FFM than non-carriers of follistatin haplotype group 1 (17.8 +/- 0.2 vs. 16.5 +/- 0.5 kg, respectively, p <0.05). Moreover, male carriers of follistatin haplotype group 3 exhibited significantly less total leg FFM than non-carriers (16.6 +/- 0.3 vs. 17.5 +/- 0.2 kg, respectively, p <0.05). No significant associations between these groups were observed in women. Conclusions. The data indicate that the ACVR2B and follistatin loci may contribute to the inter-individual variation in skeletal muscle mass and strength.
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