caa a22 4500 445861932 CHVBK 20180317145446.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00439-010-0910-8 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0910-8 AKT1 polymorphisms are associated with risk for metabolic syndrome [Elektronische Daten] [Joseph Devaney, Heather Gordish-Dressman, Brennan Harmon, Margaret Bradbury, Stephanie Devaney, Tamara Harris, Paul Thompson, Priscilla Clarkson, Thomas Price, Theodore Angelopoulos, Paul Gordon, Niall Moyna, Linda Pescatello, Paul Visich, Robert Zoeller, Richard Seip, Jinwook Seo, Bo Kim, Laura Tosi, Melissa Garcia, Rongling Li, Joseph Zmuda, Matthew Delmonico, Robert Lindsay, Barbara Howard, William Kraus, Eric Hoffman] Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n=574; age 23.7±5.7years), Strong Heart Study (SHS) (n=2,134; age 55.5±7.9years), Dynamics of Health, Aging and Body Composition (Health ABC) (n=3,075; age 73.6±2.9years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n=175; age 40-65years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p<0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p=0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations. The Author(s), 2010 Devaney Joseph Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Gordish-Dressman Heather Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Harmon Brennan Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Bradbury Margaret Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Devaney Stephanie Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Harris Tamara National Institute of Aging, National Institutes of Health, 20892, Bethesda, MD, USA aut Thompson Paul Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut Clarkson Priscilla Department of Kinesiology, University of Massachusetts, 01003, Amherst, MA, USA aut Price Thomas Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut Angelopoulos Theodore Department of Health Professions, Center for Lifestyle Medicine, University of Central Florida, 32816, Orlando, FL, USA aut Gordon Paul Laboratory for Physical Activity and Exercise Intervention Research, University of Michigan, 48108, Ann Arbor, MI, USA aut Moyna Niall Department of Sport Science and Health, Dublin City University, Dublin 9, Ireland aut Pescatello Linda School of Allied Health, University of Connecticut, 06269, Storrs, CT, USA aut Visich Paul Human Performance Laboratory, Central Michigan University, 48859, Mount Pleasant, MI, USA aut Zoeller Robert Department of Exercise Science and Health Promotion, Florida Atlantic University, 33314, Davie, FL, USA aut Seip Richard Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut Seo Jinwook Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Kim Bo INFINITT Technology, Seoul, Korea aut Tosi Laura Orthopedic Surgery and Sports Medicine, Children's National Medical Center, 20010, Washington, DC, USA aut Garcia Melissa National Institute of Aging, National Institutes of Health, 20892, Bethesda, MD, USA aut Li Rongling Department of Preventive Medicine, University of Tennessee, 39163, Memphis, TN, USA aut Zmuda Joseph Department of Epidemiology and Human Genetics, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut Delmonico Matthew Department of Kinesiology, University of Rhode Island, 02881, Kingston, RI, USA aut Lindsay Robert Faculty of Medicine, University of Glasgow, Glasgow, UK aut Howard Barbara MedStar Research Institute, 20783, Hyattsville, MD, USA aut Kraus William Duke Center for Living, Duke University Medical Center, 27710, Durham, NC, USA aut Hoffman Eric Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut Human Genetics Springer-Verlag 129/2(2011-02-01), 129-139 0340-6717 129:2<129 2011 129 439 https://doi.org/10.1007/s00439-010-0910-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0910-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Devaney Joseph Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Gordish-Dressman Heather Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Harmon Brennan Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Bradbury Margaret Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Devaney Stephanie Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Harris Tamara National Institute of Aging, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Thompson Paul Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut NATIONALLICENCE 700 1- Clarkson Priscilla Department of Kinesiology, University of Massachusetts, 01003, Amherst, MA, USA aut NATIONALLICENCE 700 1- Price Thomas Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut NATIONALLICENCE 700 1- Angelopoulos Theodore Department of Health Professions, Center for Lifestyle Medicine, University of Central Florida, 32816, Orlando, FL, USA aut NATIONALLICENCE 700 1- Gordon Paul Laboratory for Physical Activity and Exercise Intervention Research, University of Michigan, 48108, Ann Arbor, MI, USA aut NATIONALLICENCE 700 1- Moyna Niall Department of Sport Science and Health, Dublin City University, Dublin 9, Ireland aut NATIONALLICENCE 700 1- Pescatello Linda School of Allied Health, University of Connecticut, 06269, Storrs, CT, USA aut NATIONALLICENCE 700 1- Visich Paul Human Performance Laboratory, Central Michigan University, 48859, Mount Pleasant, MI, USA aut NATIONALLICENCE 700 1- Zoeller Robert Department of Exercise Science and Health Promotion, Florida Atlantic University, 33314, Davie, FL, USA aut NATIONALLICENCE 700 1- Seip Richard Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA aut NATIONALLICENCE 700 1- Seo Jinwook Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Kim Bo INFINITT Technology, Seoul, Korea aut NATIONALLICENCE 700 1- Tosi Laura Orthopedic Surgery and Sports Medicine, Children's National Medical Center, 20010, Washington, DC, USA aut NATIONALLICENCE 700 1- Garcia Melissa National Institute of Aging, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Li Rongling Department of Preventive Medicine, University of Tennessee, 39163, Memphis, TN, USA aut NATIONALLICENCE 700 1- Zmuda Joseph Department of Epidemiology and Human Genetics, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Delmonico Matthew Department of Kinesiology, University of Rhode Island, 02881, Kingston, RI, USA aut NATIONALLICENCE 700 1- Lindsay Robert Faculty of Medicine, University of Glasgow, Glasgow, UK aut NATIONALLICENCE 700 1- Howard Barbara MedStar Research Institute, 20783, Hyattsville, MD, USA aut NATIONALLICENCE 700 1- Kraus William Duke Center for Living, Duke University Medical Center, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Hoffman Eric Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave. NW, 20010, Washington, DC, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/2(2011-02-01), 129-139 0340-6717 129:2<129 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer