{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:57:44Z","timestamp":1791496664654,"version":"4.3.4"},"reference-count":28,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"German Federal Ministry of Education and Research"},{"name":"German Center for Diabetes Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all 7 AMPK subunit genes on adiposity, glucose metabolism, and lipid metabolism has not yet been systematically studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design and Methods<\/jats:title>\n                  <jats:p>A cohort of 2789 nondiabetic participants from the T\u00fcbingen Family study of type 2 diabetes, metabolically characterized by oral glucose tolerance test and genotyped by genome-wide SNP array, was analyzed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 6 largely nonoverlapping SNP sets across 4 AMPK genes (PRKAA1, PRKAA2, PRKAG2, PRKAG3) associated with adiposity, insulin sensitivity, insulin secretion, blood glucose, total\/LDL cholesterol, or HDL cholesterol, respectively. A genetic score of body-fat-increasing alleles revealed per-allele effect sizes on body mass index (BMI) of +0.22 kg\/m2 (P = 2.3 \u00d7 10\u20137), insulin sensitivity of \u22120.12 \u00d7 1019 L2\/mol2 (P = 9.9 \u00d7 10\u20136) and 2-hour blood glucose of +0.02 mmol\/L (P = 0.0048). Similar effects on blood glucose were observed with scores of insulin-sensitivity-reducing, insulin-secretion-reducing and glucose-raising alleles, respectively. A genetic cholesterol score increased total and LDL cholesterol by 1.17 mg\/dL per allele (P = 0.0002 and P = 3.2 \u00d7 10\u20135, respectively), and a genetic HDL score decreased HDL cholesterol by 0.32 mg\/dL per allele (P = 9.1 \u00d7 10\u20136).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We describe largely nonoverlapping genetic determinants in AMPK genes for diabetes-\/atherosclerosis-related traits, which reflect the metabolic pathways controlled by the enzyme. Formation of trait-specific genetic scores revealed additivity of allele effects, with body-fat-raising alleles reaching a marked effect size. (J Clin Endocrinol Metab 105: 14\u201325, 2020)<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz020","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T03:17:20Z","timestamp":1576207040000},"page":"14-25","source":"Crossref","is-referenced-by-count":16,"title":["AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism"],"prefix":"10.1210","volume":"105","author":[{"given":"Elko","family":"Randrianarisoa","sequence":"first","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD), 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lehn-Stefan","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and 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Genetics, Helmholtz Center Munich, 85764 Neuherberg, Germany"},{"name":"Chair of Experimental Genetics, Technical University Munich, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fritsche","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD), 72076 T\u00fcbingen, Germany"},{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, Eberhard Karls University T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Ulrich","family":"H\u00e4ring","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of T\u00fcbingen, 72076 T\u00fcbingen, 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