Genetic Modifiers of Cardiorespiratory Fitness Response to Lifestyle Intervention
Identifieur interne : 005454 ( Main/Exploration ); précédent : 005453; suivant : 005455Genetic Modifiers of Cardiorespiratory Fitness Response to Lifestyle Intervention
Auteurs : Inga Peter [États-Unis] ; George D. Papandonatos [États-Unis] ; L. Maria Belalcazar [États-Unis] ; YAO YANG [États-Unis] ; Bahar Erar [États-Unis] ; John M. Jakicic [États-Unis] ; Jessica L. Unick [États-Unis] ; Ashok Balasubramanyam [États-Unis] ; Edward W. Lipkin [États-Unis] ; Linda M. Delahanty [États-Unis] ; Lynne E. Wagenknecht [États-Unis] ; Rena R. Wing [États-Unis] ; Jeanne M. Mccaffery [États-Unis] ; Gordon S. Huggins [États-Unis]Source :
- Medicine and science in sports and exercise [ 0195-9131 ] ; 2014.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Génétique.
English descriptors
- KwdEn :
Abstract
Purpose: Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type 2 diabetes risk and delays disease progression. We hypothesized that genetic variants modify fitness response to an intensive lifestyle intervention (ILI) in the Action for Health in Diabetes (Look AHEAD) randomized clinical trial, aimed to detect whether ILI will reduce cardiovascular events in overweight/obese subjects with type 2 diabetes compared with a standard of care. Methods: Polymorphisms in established fitness genes and in all loci assayed on the Illumina CARe iSelect chip were examined as predictors of change in MET level, estimated using a treadmill test, in response to a 1-yr intervention in 3899 participants. Results: We identified a significant signal in previously reported fitness-related gene RUNXI that was associated with 1-yr METs response in ILI (0.19 ± 0.04 MET less improvement per minor allele copy; P= 1.9 × 10-5) and genotype-intervention interaction (P = 4.8 × 10-3). In the chipwide analysis, FKBP7 rs17225700 showed a significant association with ILI response among subjects not receiving beta-blocker medications (0.47 ± 0.09 METs less improvement; P = 5.3 × 10-7) and genotype-treatment interaction (P = 5.3 × 10-5). The Gene Relationships Among Implicated Loci pathway-based analysis identified connections between associated genes, including those influencing vascular tone, muscle contraction, cardiac energy substrate dynamics, and muscle protein synthesis. Conclusions: This is the first study to identify genetic variants associated with fitness responses to a randomized lifestyle intervention in overweight/obese diabetic individuals. RUNX1 and FKBP7, involved in erythropoesis and muscle protein synthesis, respectively, are related to change in cardiorespiratory fitness in response to exercise.
Affiliations:
- États-Unis
- Pennsylvanie, Rhode Island, Texas, Washington (État)
- Houston, Pittsburgh, Providence (Rhode Island), Seattle
- Baylor College of Medicine, Université Brown, Université de Pittsburgh, Université de Washington
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Lipkin</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Division of Metabolism, Endocrinology and Nutrition, University of Washington</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Seattle</settlement><region type="state">Washington (État)</region></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Delahanty, Linda M" sort="Delahanty, Linda M" uniqKey="Delahanty L" first="Linda M." last="Delahanty">Linda M. Delahanty</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Diabetes Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author><author><name sortKey="Wagenknecht, Lynne E" sort="Wagenknecht, Lynne E" uniqKey="Wagenknecht L" first="Lynne E." last="Wagenknecht">Lynne E. Wagenknecht</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Division of Public Health Sciences, Wake Forest School of Medicine</s1><s2>Winston-Salem, NC</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Winston-Salem, NC</wicri:noRegion></affiliation></author><author><name sortKey="Wing, Rena R" sort="Wing, Rena R" uniqKey="Wing R" first="Rena R." last="Wing">Rena R. Wing</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Providence, RI</wicri:noRegion></affiliation></author><author><name sortKey="Mccaffery, Jeanne M" sort="Mccaffery, Jeanne M" uniqKey="Mccaffery J" first="Jeanne M." last="Mccaffery">Jeanne M. Mccaffery</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Providence, RI</wicri:noRegion></affiliation></author><author><name sortKey="Huggins, Gordon S" sort="Huggins, Gordon S" uniqKey="Huggins G" first="Gordon S." last="Huggins">Gordon S. Huggins</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Molecular Cardiology Research Institute, Center for Translational Genomics, Tufts Medical Center and Tufts University</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0059249</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0059249 INIST</idno><idno type="RBID">Pascal:14-0059249</idno><idno type="wicri:Area/PascalFrancis/Corpus">000F05</idno><idno type="wicri:Area/PascalFrancis/Curation">003699</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000822</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000822</idno><idno type="wicri:doubleKey">0195-9131:2014:Peter I:genetic:modifiers:of</idno><idno type="wicri:Area/Main/Merge">005745</idno><idno type="wicri:Area/Main/Curation">005454</idno><idno type="wicri:Area/Main/Exploration">005454</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Genetic Modifiers of Cardiorespiratory Fitness Response to Lifestyle Intervention</title><author><name sortKey="Peter, Inga" sort="Peter, Inga" uniqKey="Peter I" first="Inga" last="Peter">Inga Peter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine</s1><s2>New York, NY</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>New York, NY</wicri:noRegion></affiliation></author><author><name sortKey="Papandonatos, George D" sort="Papandonatos, George D" uniqKey="Papandonatos G" first="George D." last="Papandonatos">George D. Papandonatos</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Statistical Sciences, Brown University</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Providence (Rhode Island)</settlement><region type="state">Rhode Island</region></placeName><orgName type="university">Université Brown</orgName></affiliation></author><author><name sortKey="Belalcazar, L Maria" sort="Belalcazar, L Maria" uniqKey="Belalcazar L" first="L. Maria" last="Belalcazar">L. Maria Belalcazar</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Medicine, University of Texas Medical Branch</s1><s2>Galveston, TX</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Galveston, TX</wicri:noRegion></affiliation></author><author><name sortKey="Yao Yang" sort="Yao Yang" uniqKey="Yao Yang" last="Yao Yang">YAO YANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine</s1><s2>New York, NY</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>New York, NY</wicri:noRegion></affiliation></author><author><name sortKey="Erar, Bahar" sort="Erar, Bahar" uniqKey="Erar B" first="Bahar" last="Erar">Bahar Erar</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Statistical Sciences, Brown University</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Providence (Rhode Island)</settlement><region type="state">Rhode Island</region></placeName><orgName type="university">Université Brown</orgName></affiliation></author><author><name sortKey="Jakicic, John M" sort="Jakicic, John M" uniqKey="Jakicic J" first="John M." last="Jakicic">John M. Jakicic</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Health and Physical Activity, Physical Activity and Weight Management Research Center, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Unick, Jessica L" sort="Unick, Jessica L" uniqKey="Unick J" first="Jessica L." last="Unick">Jessica L. Unick</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Providence, RI</wicri:noRegion></affiliation></author><author><name sortKey="Balasubramanyam, Ashok" sort="Balasubramanyam, Ashok" uniqKey="Balasubramanyam A" first="Ashok" last="Balasubramanyam">Ashok Balasubramanyam</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Translational Metabolism Unit, Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine</s1><s2>Houston, TX</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Lipkin, Edward W" sort="Lipkin, Edward W" uniqKey="Lipkin E" first="Edward W." last="Lipkin">Edward W. Lipkin</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Division of Metabolism, Endocrinology and Nutrition, University of Washington</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Seattle</settlement><region type="state">Washington (État)</region></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Delahanty, Linda M" sort="Delahanty, Linda M" uniqKey="Delahanty L" first="Linda M." last="Delahanty">Linda M. Delahanty</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Diabetes Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author><author><name sortKey="Wagenknecht, Lynne E" sort="Wagenknecht, Lynne E" uniqKey="Wagenknecht L" first="Lynne E." last="Wagenknecht">Lynne E. Wagenknecht</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Division of Public Health Sciences, Wake Forest School of Medicine</s1><s2>Winston-Salem, NC</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Winston-Salem, NC</wicri:noRegion></affiliation></author><author><name sortKey="Wing, Rena R" sort="Wing, Rena R" uniqKey="Wing R" first="Rena R." last="Wing">Rena R. Wing</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Providence, RI</wicri:noRegion></affiliation></author><author><name sortKey="Mccaffery, Jeanne M" sort="Mccaffery, Jeanne M" uniqKey="Mccaffery J" first="Jeanne M." last="Mccaffery">Jeanne M. Mccaffery</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Weight Control and Diabetes Research Center, Department of Psychiatry and Human Behavior, The Miriam Hospital and Brown Medical School</s1><s2>Providence, RI</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Providence, RI</wicri:noRegion></affiliation></author><author><name sortKey="Huggins, Gordon S" sort="Huggins, Gordon S" uniqKey="Huggins G" first="Gordon S." last="Huggins">Gordon S. Huggins</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Molecular Cardiology Research Institute, Center for Translational Genomics, Tufts Medical Center and Tufts University</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Medicine and science in sports and exercise</title><title level="j" type="abbreviated">Med. sci. sports exerc.</title><idno type="ISSN">0195-9131</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Medicine and science in sports and exercise</title><title level="j" type="abbreviated">Med. sci. sports exerc.</title><idno type="ISSN">0195-9131</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cardiovascular risk</term><term>Care</term><term>Circulatory system</term><term>Clinical trial</term><term>Genetics</term><term>Genotype</term><term>Interaction</term><term>Life style</term><term>Respiratory system</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Génétique</term><term>Appareil circulatoire</term><term>Appareil respiratoire</term><term>Risque cardiovasculaire</term><term>Mode de vie</term><term>Essai clinique</term><term>Soin</term><term>Génotype</term><term>Traitement</term><term>Interaction</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Purpose: Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type 2 diabetes risk and delays disease progression. We hypothesized that genetic variants modify fitness response to an intensive lifestyle intervention (ILI) in the Action for Health in Diabetes (Look AHEAD) randomized clinical trial, aimed to detect whether ILI will reduce cardiovascular events in overweight/obese subjects with type 2 diabetes compared with a standard of care. Methods: Polymorphisms in established fitness genes and in all loci assayed on the Illumina CARe iSelect chip were examined as predictors of change in MET level, estimated using a treadmill test, in response to a 1-yr intervention in 3899 participants. Results: We identified a significant signal in previously reported fitness-related gene RUNXI that was associated with 1-yr METs response in ILI (0.19 ± 0.04 MET less improvement per minor allele copy; P= 1.9 × 10<sup>-5</sup>) and genotype-intervention interaction (P = 4.8 × 10<sup>-3</sup>). In the chipwide analysis, FKBP7 rs17225700 showed a significant association with ILI response among subjects not receiving beta-blocker medications (0.47 ± 0.09 METs less improvement; P = 5.3 × 10<sup>-7</sup>) and genotype-treatment interaction (P = 5.3 × 10<sup>-5</sup>). The Gene Relationships Among Implicated Loci pathway-based analysis identified connections between associated genes, including those influencing vascular tone, muscle contraction, cardiac energy substrate dynamics, and muscle protein synthesis. Conclusions: This is the first study to identify genetic variants associated with fitness responses to a randomized lifestyle intervention in overweight/obese diabetic individuals. RUNX1 and FKBP7, involved in erythropoesis and muscle protein synthesis, respectively, are related to change in cardiorespiratory fitness in response to exercise.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li><li>Rhode Island</li><li>Texas</li><li>Washington (État)</li></region><settlement><li>Houston</li><li>Pittsburgh</li><li>Providence (Rhode Island)</li><li>Seattle</li></settlement><orgName><li>Baylor College of Medicine</li><li>Université Brown</li><li>Université de Pittsburgh</li><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Peter, Inga" sort="Peter, Inga" uniqKey="Peter I" first="Inga" last="Peter">Inga Peter</name></noRegion><name sortKey="Balasubramanyam, Ashok" sort="Balasubramanyam, Ashok" uniqKey="Balasubramanyam A" first="Ashok" last="Balasubramanyam">Ashok Balasubramanyam</name><name sortKey="Belalcazar, L Maria" sort="Belalcazar, L Maria" uniqKey="Belalcazar L" first="L. Maria" last="Belalcazar">L. Maria Belalcazar</name><name sortKey="Delahanty, Linda M" sort="Delahanty, Linda M" uniqKey="Delahanty L" first="Linda M." last="Delahanty">Linda M. Delahanty</name><name sortKey="Erar, Bahar" sort="Erar, Bahar" uniqKey="Erar B" first="Bahar" last="Erar">Bahar Erar</name><name sortKey="Huggins, Gordon S" sort="Huggins, Gordon S" uniqKey="Huggins G" first="Gordon S." last="Huggins">Gordon S. Huggins</name><name sortKey="Jakicic, John M" sort="Jakicic, John M" uniqKey="Jakicic J" first="John M." last="Jakicic">John M. Jakicic</name><name sortKey="Lipkin, Edward W" sort="Lipkin, Edward W" uniqKey="Lipkin E" first="Edward W." last="Lipkin">Edward W. Lipkin</name><name sortKey="Mccaffery, Jeanne M" sort="Mccaffery, Jeanne M" uniqKey="Mccaffery J" first="Jeanne M." last="Mccaffery">Jeanne M. Mccaffery</name><name sortKey="Papandonatos, George D" sort="Papandonatos, George D" uniqKey="Papandonatos G" first="George D." last="Papandonatos">George D. Papandonatos</name><name sortKey="Unick, Jessica L" sort="Unick, Jessica L" uniqKey="Unick J" first="Jessica L." last="Unick">Jessica L. Unick</name><name sortKey="Wagenknecht, Lynne E" sort="Wagenknecht, Lynne E" uniqKey="Wagenknecht L" first="Lynne E." last="Wagenknecht">Lynne E. Wagenknecht</name><name sortKey="Wing, Rena R" sort="Wing, Rena R" uniqKey="Wing R" first="Rena R." last="Wing">Rena R. Wing</name><name sortKey="Yao Yang" sort="Yao Yang" uniqKey="Yao Yang" last="Yao Yang">YAO YANG</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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