Literature DB >> 18541994

New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function.

John R B Perry1, Timothy M Frayling.   

Abstract

PURPOSE OF REVIEW: Over the past 18 months, the number of gene loci robustly associated with type 2 diabetes has risen from three to 18. In this study, we focus on explaining the genome-wide approach that has led to most of these discoveries and discuss some of the early insights the new gene loci have provided into the aetiology of type 2 diabetes. RECENT
FINDINGS: Recent genome-wide association studies have provided an important resource for furthering our understanding of type 2 diabetes disease mechanisms. Genes previously unsuspected of playing a role in diabetes are now implicated in the disease process. These include genes in cell cycling control (CDKN2A/2B, CDKAL1), transcription factors (TCF7L2, HHEX), and ion channels (SLC30A8). These variants are all associated with insulin-secretory defects in the general population and show little if any relationship to insulin resistance. Two common variants (near or in FTO and MC4R) alter diabetes risk through a primary effect on obesity.
SUMMARY: Recent genome-wide association studies show that there are now 18 gene loci associated with the risk of type 2 diabetes. Most of these T2D gene loci affect insulin secretion.

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Year:  2008        PMID: 18541994     DOI: 10.1097/MCO.0b013e32830349a1

Source DB:  PubMed          Journal:  Curr Opin Clin Nutr Metab Care        ISSN: 1363-1950            Impact factor:   4.294


  44 in total

1.  Do insulinotropic glucose-lowering drugs do more harm than good? The hypersecretion hypothesis revisited.

Authors:  I Rustenbeck; S Baltrusch; M Tiedge
Journal:  Diabetologia       Date:  2010-07-01       Impact factor: 10.122

Review 2.  Type 2 diabetes and obesity: genomics and the clinic.

Authors:  Mary E Travers; Mark I McCarthy
Journal:  Hum Genet       Date:  2011-06-07       Impact factor: 4.132

3.  The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients.

Authors:  Carina Zabena; José L González-Sánchez; María T Martínez-Larrad; Antonio Torres-García; Jesús Alvarez-Fernández-Represa; Arturo Corbatón-Anchuelo; Milagros Pérez-Barba; Manuel Serrano-Ríos
Journal:  Obes Surg       Date:  2008-10-15       Impact factor: 4.129

Review 4.  Metabolic syndrome: from epidemiology to systems biology.

Authors:  Aldons J Lusis; Alan D Attie; Karen Reue
Journal:  Nat Rev Genet       Date:  2008-11       Impact factor: 53.242

5.  Genetic polymorphisms of diabetes-related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project.

Authors:  Humberto Parada; Rebecca J Cleveland; Kari E North; June Stevens; Susan L Teitelbaum; Alfred I Neugut; Regina M Santella; Maria E Martinez; Marilie D Gammon
Journal:  Mol Carcinog       Date:  2018-12-11       Impact factor: 4.784

6.  Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study.

Authors:  Intissar Ezzidi; Nabil Mtiraoui; Stéphane Cauchi; Emmanuel Vaillant; Aurélie Dechaume; Molka Chaieb; Maha Kacem; Wassim Y Almawi; Philippe Froguel; Touhami Mahjoub; Martine Vaxillaire
Journal:  BMC Med Genet       Date:  2009-04-15       Impact factor: 2.103

7.  Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance.

Authors:  Dennis T Villareal; Joseph C Koster; Heather Robertson; Alejandro Akrouh; Kazuaki Miyake; Graeme I Bell; Bruce W Patterson; Colin G Nichols; Kenneth S Polonsky
Journal:  Diabetes       Date:  2009-06-02       Impact factor: 9.461

8.  Common genetic determinants of glucose homeostasis in healthy children: the European Youth Heart Study.

Authors:  Clara Kelliny; Ulf Ekelund; Lars Bo Andersen; Soren Brage; Ruth J F Loos; Nicholas J Wareham; Claudia Langenberg
Journal:  Diabetes       Date:  2009-09-09       Impact factor: 9.461

9.  Combined risk allele score of eight type 2 diabetes genes is associated with reduced first-phase glucose-stimulated insulin secretion during hyperglycemic clamps.

Authors:  Leen M 't Hart; Annemarie M Simonis-Bik; Giel Nijpels; Timon W van Haeften; Silke A Schäfer; Jeanine J Houwing-Duistermaat; Dorret I Boomsma; Marlous J Groenewoud; Erwin Reiling; Els C van Hove; Michaela Diamant; Mark H H Kramer; Robert J Heine; J Antonie Maassen; Kerstin Kirchhoff; Fausto Machicao; Hans-Ulrich Häring; P Eline Slagboom; Gonneke Willemsen; Elisabeth M Eekhoff; Eco J de Geus; Jacqueline M Dekker; Andreas Fritsche
Journal:  Diabetes       Date:  2009-10-06       Impact factor: 9.461

10.  Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men.

Authors:  Alena Stancáková; Teemu Kuulasmaa; Jussi Paananen; Anne U Jackson; Lori L Bonnycastle; Francis S Collins; Michael Boehnke; Johanna Kuusisto; Markku Laakso
Journal:  Diabetes       Date:  2009-06-05       Impact factor: 9.461

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