Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

The Journal of Clinical Investigation
Joshua W KnowlesThomas Quertermous

Abstract

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decrea...Continue Reading

References

Sep 1, 1982·Clinical Pharmacokinetics·W Kalow
May 12, 1997·Mutation Research·D M GrantR Grewal
Aug 26, 1998·The Journal of Clinical Endocrinology and Metabolism·J YipG M Reaven
Oct 30, 1998·Journal of Hypertension·E Ferrannini, A Mari
Aug 15, 2001·The Journal of Clinical Endocrinology and Metabolism·F S FacchiniG M Reaven
Aug 13, 1960·British Medical Journal·D A EVANSV A McKUSICK
Oct 19, 2006·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A Bosy-WestphalM J Müller
Apr 13, 2007·Expert Opinion on Drug Metabolism & Toxicology·Edith SimElizabeth Fullam
Oct 25, 2007·Diabetic Medicine : a Journal of the British Diabetic Association·L J Rasmussen-TorvikA R Sinaiko
Mar 13, 2008·Pharmacogenetics and Genomics·David W HeinEdith Sim
Jul 22, 2008·Drug Metabolism Reviews·Edith SimSotiria Boukouvala
Aug 6, 2008·Current Drug Metabolism·Jason M WalravenDavid W Hein
Sep 6, 2008·PloS One·Francesca LucaAndrea Novelletto
Oct 29, 2009·American Journal of Physiology. Endocrinology and Metabolism·Patrick YuePhilip S Tsao
Jun 29, 2010·Nature Genetics·Benjamin F VoightUNKNOWN GIANT Consortium
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Oct 12, 2010·Nature Genetics·Elizabeth K SpeliotesRuth J F Loos
Nov 5, 2010·Endocrinology·Patrick YuePhilip S Tsao
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Apr 23, 2011·Diabetes Technology & Therapeutics·Amy B BlodgettNiloofar M Tabatabai
May 17, 2011·Nature Genetics·Karsten SuhreMatthias Nauck
Aug 2, 2011·The Journal of Clinical Investigation·Indumathi ChennamsettyGert M Kostner
Sep 3, 2011·Nature·Karsten SuhreChristian Gieger
Aug 14, 2012·Nature Genetics·Andrew P MorrisUNKNOWN DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium

❮ Previous
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Citations

Oct 6, 2016·Cell Reports·Indumathi ChennamsettyJoshua W Knowles
Mar 10, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Vanessa D de MelloJussi Pihlajamäki
Oct 5, 2017·Human Molecular Genetics·Eleanor WheelerInês Barroso
Mar 7, 2018·American Journal of Physiology. Endocrinology and Metabolism·Erika M RipleyRalph A DeFronzo
Feb 2, 2018·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Jul 22, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Ivan Carcamo-OriveJoshua W Knowles
May 28, 2016·Circulation Research·Joshua A Beckman, Mark A Creager
Feb 1, 2019·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Aug 25, 2017·Cell Death & Disease·Shi ChenFeng Gao
May 10, 2019·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Jeffrey I MechanickGuillermo E Umpierrez
Aug 2, 2018·Physiological Reviews·Max C Petersen, Gerald I Shulman
Jan 30, 2020·Circulation·Salim S ViraniUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
May 27, 2017·Current Opinion in Ophthalmology·Yu-Hung Lai, Kwou-Yeung Wu
Feb 16, 2020·Endocrinology·Panjamaporn SangwungJoshua W Knowles
Mar 21, 2020·Nature Communications·Mohsen FathzadehJoshua W Knowles
Dec 15, 2017·Proceedings of the National Academy of Sciences of the United States of America·João Paulo CamporezGerald I Shulman
Dec 6, 2019·Nature·Michael Roden, Gerald I Shulman
Jun 18, 2016·Current Cardiology Reports·Audrey E Brown, Mark Walker
Apr 4, 2017·International Journal of Epidemiology·Chih-Cheng HsuChao A Hsiung
Sep 24, 2020·International Journal of Molecular Sciences·Yulia A NasykhovaAndrey S Glotov
Dec 3, 2020·Drug Metabolism Reviews·Philip G Board, M W Anders
Jan 28, 2021·Circulation·Salim S ViraniUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Oct 22, 2020·Toxicology Reports·Kyung U HongDavid W Hein
Oct 16, 2020·Cell·Lifeng WangAnders M Näär
Nov 24, 2021·Annual Review of Genetics·Daichao XuJunying Yuan

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Methods Mentioned

BETA
genotyping
coronary artery disease
acetylation
acetylator
transfection
flow cytometry
PCR
ELISA

Software Mentioned

IMPUTE
GraphPad Prism
MiniMac
MACH
EIGENSTRAT
relative expression software tool ( REST
METAL
STATA
GLGC
MAGIC

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