title: IGF-II gene region polymorphisms related to exertional muscle damage.
abstract: We examined the association of a novel single-nucleotide polymorphism (SNP) in IGF-I (IGF-I -C1245T located in the promoter) and eight SNPs in the IGF-II gene region with indicators of muscle damage [strength loss, muscle soreness, and increases in circulating levels of creatine kinase (CK) and myoglobin] after eccentric exercise. We also examined two SNPs in the IGF binding protein-3 (IGFBP-3). The age, height, and body mass of the 151 subjects studied were 24.1 +/- 5.2 yr, 170.8 +/- 9.9 cm, and 73.3 +/- 17.0 kg, respectively. There were no significant associations of phenotypes with IGF-I. IGF-II SNP (G12655A, rs3213216) and IGFBP-3 SNP (A8618T, rs6670) were not significantly associated with any variable. The most significant finding in this study was that for men, IGF-II (C13790G, rs3213221), IGF-II (ApaI, G17200A, rs680), IGF-II antisense (IGF2AS) (G11711T, rs7924316), and IGFBP-3 (-C1592A, rs2132570) were significantly associated with muscle damage indicators. We found that men who were 1) homozygous for the rare IGF-II C13790G allele and rare allele for the ApaI (G17200A) SNP demonstrated the greatest strength loss immediately after exercise, greatest soreness, and highest postexercise serum CK activity; 2) homozygous wild type for IGF2AS (G11711T, rs7924316) had the greatest strength loss and most muscle soreness; and 3) homozygous wild type for the IGF2AS G11711T SNP showed the greatest strength loss, highest muscle soreness, and greater CK and myoglobin response to exercise. In women, fewer significant associations appeared.
authors.affiliation: Children's National Medical Center, Washington, District of Columbia, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.forename: Amy
authors.initials: A
authors.lastname: Kearns
authors.forename: Edward
authors.initials: E
authors.lastname: Zambraski
authors.forename: Priscilla M
authors.initials: PM
authors.lastname: Clarkson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D052283:Creatine Kinase, MM Form / Q000097:blood; D015444:Exercise; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D053580:Muscle Strength / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology / Q000503:physiopathology*; D009135:Muscular Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009211:Myoglobin / Q000097:blood; D010146:Pain / Q000235:genetics; D010147:Pain Measurement; D010641:Phenotype; D005082:Physical Exertion; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D009211:Myoglobin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D052283:Creatine Kinase, MM Form