title: Common genetic variation in the IGF1 associates with maximal force output.
abstract: OBJECTIVE
  We clarified the effect of insulin-like growth factor-1 (IGF1), IGF-binding protein-3 (IGFBP3), interleukin-6 (IL6), and its receptor (IL6R) gene variants on muscular and aerobic performance, body composition, and on circulating levels of IGF-1 and IL-6. Single nucleotide polymorphisms (SNPs) may, in general, influence gene regulation or its expression, or the structure and function of the corresponding protein, and modify its biological effects. IGF-1 is involved in the anabolic pathways of skeletal muscle. IL-6 plays an important role in muscle energy homeostasis during strenuous physical exercise.
  
  
  METHODS
  Eight hundred forty-one healthy Finnish male subjects of Caucasian origin were genotyped for IGF1 (rs6220 and rs7136446), IGFBP3 (rs2854744), IL6 (rs1800795), and IL6R (rs4537545) SNPs, and studied for associations with maximal force of leg extensor muscles, maximal oxygen consumption, body fat percent, and IGF-1 and IL-6 levels. Analytic methods included dynamometer, bicycle ergometer, bioimpedance, ELISA, and polymerase chain reaction assays.
  
  
  RESULTS
  All investigated SNPs conformed to Hardy-Weinberg equilibrium with allele frequencies validated against CEU population. Genotype CC of rs7136446 associated with higher body fat and increased maximal force production. Genotype CC of the IGFBP3 SNP rs2854744 and TT genotype of the IL6R SNP rs4537545 associated with higher IL-6 levels. In logistic regression analysis, allele C of the rs2854744 decreased odds for lower body fat. None of the studied SNPs associated with aerobic performance.
  
  
  CONCLUSIONS
  Our data suggest that common variation in the IGF1 gene may affect maximal force production, which can be explained by the role of IGF-1 in the anabolic pathways of muscle and neurotrophy. Variations in the IGF1 and IGFBP3 gene may result in higher body fat and be related to alterations of IGF-1-mediated tissue growth.
authors.affiliation: Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Huuskonen
authors.forename: Jani
authors.initials: J
authors.lastname: Lappalainen
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.forename: Matti
authors.initials: M
authors.lastname: Santtila
authors.forename: Keijo
authors.initials: K
authors.lastname: Häkkinen
authors.forename: Heikki
authors.initials: H
authors.lastname: Kyröläinen
authors.forename: Mustafa
authors.initials: M
authors.lastname: Atalay
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000328:Adult; D015992:Body Mass Index; D014644:Genetic Variation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007866:Leg / Q000502:physiology; D008297:Male; D053580:Muscle Strength / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics; D055815:Young Adult
chemical_list: C515497:IGFBP3 protein, human; C508600:IL6 protein, human; C508603:IL6R protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D007334:Insulin-Like Growth Factor I