A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia.

Autor: Simeone CA; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA., Wilkerson JL; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Poss AM; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Banks JA; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Varre JV; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Guevara JL; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA., Hernandez EJ; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Utah Center for Genetic Discovery, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Gorsi B; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Utah Center for Genetic Discovery, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Atkinson DL; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Turapov T; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Frodsham SG; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA., Morales JCF; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA., O'Neil K; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA, 02115, USA., Moore B; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Utah Center for Genetic Discovery, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Yandell M; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.; Utah Center for Genetic Discovery, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Summers SA; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Krolewski AS; Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Holland WL; Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, 84112, USA., Pezzolesi MG; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA. marcus.pezzolesi@hsc.utah.edu.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA. marcus.pezzolesi@hsc.utah.edu.; Diabetes and Metabolism Research Center, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA. marcus.pezzolesi@hsc.utah.edu.
Jazyk: angličtina
Zdroj: NPJ genomic medicine [NPJ Genom Med] 2022 Jul 22; Vol. 7 (1), pp. 43. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1038/s41525-022-00314-z
Abstrakt: Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring a 10-nucleotide deletion mutation in ADIPOQ that cosegregates with diabetes and end-stage renal disease. This mutation introduces a frameshift in exon 3, resulting in a premature termination codon that disrupts translation of adiponectin's globular domain. Subjects with the mutation had dramatically reduced circulating adiponectin and increased long-chain ceramides levels. Functional studies suggest that the mutated protein acts as a dominant negative through its interaction with non-mutated adiponectin, decreasing circulating adiponectin levels, and correlating with metabolic disease.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: