Tab. 2 Komplette Liste der mit Typ-2-Diabetes assoziierten Gene

Transkript

1 Tab. 2 Komplette Liste der mit assoziierten Gene Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung NOTCH2 Neurogenic locus notch homolog protein 2 1p13-p11 rs ka -Metaanalyse 2008 [1][22][25][30] PROX1 Prospero-related homeobox 1 1q32.2-q32.3 rs [5][22][25] BCL11A B-cell cll/lymphoma 11A 2p16.1 rs ka -Metaanalyse THADA Thyroid adenoma-associated gene 2p21 rs ( ) zweite Phase Insulinsekre -Metaanalyse 2008 [1][22][25][30] GCKR Glucokinase regulatory protein 2p23 rs RBMS1 RNA-binding motif protein,single 2q24.2 rs strand-interacting ( ) GLP-1 und argininstimulierte Insulinantwort (+) Insulinresistenz (+) Nüchterninsulin (+) 2-h-Glukose Glukoseregula in Leber ka 2010 [1][5][16][22][25] -Metaanalyse 2010 [13][22] G6PC2 Glucose-6-phosphatase,catalytic 2 2q31.1 rs für verwandte Merkmale 2010 [5][25][27] IRS1 Insulin receptor substrate 1 2q36 rs (+) Insulinresistenz (+) Nüchterninsulin (+) 2-h-Insulin Einzel [1][14][22][25]

2 Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung ADAMTS9 UBE2E2 PPARG ADCY5 IGF2BP2 WFS1 ZBED3 CDKAL1 JAZF1 A disintegrin-like and metalloproteinase with thrombospondin type 1 motif, 9 Ubiquitin-conjugating enzyme e2e 2 Peroxisome proliferator-activated rezeptor gamma Adenylate cyclase 5 Insulin-like growth factor 2 mrnabinding protein 2 Wolfram syndrome 1 Zinc finger bed domain-containing protein 3 CDK5 regulatory subunit-associated protein 1-like 1 Juxtaposed with another zinc finger gene 1 3p14.3-p14.2 3p24.3 3p25 3q13.2-q21 3q27.2 4p16 5q13.3 6p22.3 7p15.2-p15.1 rs rs rs rs rs rs Spielt wichtige Rolle bei der Insulinsynthese und -sekre unter Bedingungen, bei denen der ER-Stress in β-zellen angestiegen ist Insulinresistenz ( ) Insulinclearance (+) 2-h-Glukose -Metaanalyse 2008 [1][22][25][27][30] Einzel [11][22][28] Kandidatengenassozia 2000 [1][10][11][17][22] 2010 [1][16][22] Einzel [1][3][10][17][22][31] Kandidatengenassozia rs ka -Metaanalyse rs rs ( ) β-zell-masse ( ) Proinsulinkonversa (+) Insulinsekre (+) Nüchterninsulin 2007 [1][15][22][25] Einzel [1][2][3][10][11][17][20][22] [27][31] -Metaanalyse 2008 [1][22][25][30]

3 Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung GCK DGKB/ TMEM195 KLF14 TP53INP1 SLC30A8 CDKN2A/C DKN2B PTPRD CHCHD9 Glucokinase Diacylglycerol kinase, beta 90 kda/ transmembrane protein 195 Kruppel-like factor 14 Tumor protein p53-inducible nuclear protein 1 Solute carrier family 30 (zinc transporter), member 8 Cyclin-dependent kinase inhibitor 2A/2B Proteintyrosine phosphatase,receptortype; delta Coiled-coil-helix-coiled-coil-helix domain containing 9 7p13 7p21.2 7q32.3 8q22.1 8q p21 9p24-p23 9q21.31 rs rs rs rs rs rs rs rs (+) glykolisiertes Hämaglobin regulierendes Enzym bei der Insulinfreisetzung (+) Nüchterninsulin ka ( ) Proinsulinkonversa (+) 2-h-Glukose (+) glykolisiertes Hämaglobin ( ) β-zell-masse Einfluss auf Insulinsignalweg ka 2010 [1][5][22][25] 2010 [1][5][22][25] -Metaanalyse 2010 [19][22][26] -Metaanalyse Einzel [1][3][9][10][17][18][22][31] Einzel [1][3][10][11][17][22][25] [31] Einzel [1][22][23] -Metaanalyse

4 Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung CDC123/CA MK1D HHEX/IDE/K IF11 TCF7L2 KCNJ11 ABCC8 KCNQ1 DUSP8 Cell division cycle 123 homolog/ calcium calmodulin-dependent protein kinase type 1D Hematopoietically expressed homeobox/insulin-degrading enzyme/kinesin family member 11 Transcrrip factor 7-like 2 Potassium inwardly,rectifying channel; subfamily j, member 11 ATP-binding cassette,subfamily c,member 8 Potassium channel, voltage-gated, kqt-like subfamily, member 1 Dual-specificity phosphatase 8 10p13 10q q p p p p15.5 rs rs rs rs5219 ( ) Proinsulinkonversa ( ) insulindegradierendes Enzym ( ) inkretinstimulierte Insulinsekre ( ) Proinsulinkonversa (+) 2-h-Glukose ( ) Glukagonsuppression -Metaanalyse 2008 [1][22][30] Einzel [1][3][10][11][17][18][22] [25][31] Verknüpfungsanalysen 2006 [1][2][6][8][10][16][17][18] Kandidatengenassozia rs Einfluss auf Insulinsekre Kandidatengenassozia rs ( ) Inkretinsekre -Metaanalyse rs ka Einzel- [22] 2003 [1][10][11][17][22] 2003 [22][25] 2008/2010 [1][22][24][26][29] [22][25]

5 Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung CENTD2 MTNR1B TSPAN8/LG R5 HMGA2 HNF1A C2CD4A/B ZFAND6 Centaurin, delta-2 Melatonin receptor 1B Tetraspanin 8/ leucine-rich repeatcontaining g protein-coupled receptor 5 High mobility group at-hook 2 Hepatocyte nuclear factor-1-alpha C2 calcium-dependent domaincontaining protein 4A/B Zinc finger an1-type domaincontaining protein 6 PRC1 Protein regulating cytokinesis 1 FTO HNF1B (=TCF2) SRR Fat mass- and obesity-associated gene Hepatocyte nuclear factor-1-beta Serine racemase 11q q21-q22 12q14.1- q21.1/12q22- q23 12q q24 15q q q q cen-q p13.3 rs rs rs ( ) Nüchterninsulin β-zell-dysfunk (+) glykolisiertes Hämaglobin -Metaanalyse -Metaanalyse rs ka -Metaanalyse rs Abnormalitäten in der GSIS -Metaanalyse rs ( ) HOMO-B ( ) 2-h-Glukose Einzel- rs ka -Metaanalyse rs ka -Metaanalyse rs (+) Risiko für Fettleibigkeit (+) BMI (+) Fettmasse (+) Triglyzeride und Cholesterol Einzel- rs Kandidatengenassozia rs Beeinflusst die Insulin- und Glukagonsekre Einzel [1][5][12][22][25] 2008 [1][22][25][30] 2010 [22][25] 2010 [21][22] 2007 [1][2][4][17][22][25] 2007 [1][7][22][25] [1][22][23]

6 Gen Vollständiger Name Chromosom SNP Funk bei Ansatz Jahr der Entdeckung DUSP9 Dual-specificity phosphatase 9 Xq28 rs ka -Metaanalyse 2010 [22][26] In der Tabelle sind die derzeit bekannten -assoziierten Gene aufgelistet [22]. Es ist jeweils das Gen, der vollständige Name, die Chromosomenposi, ein bekannter SNP, die Funk mit der Genvarianten assoziiert sind, der Ansatz, in dem die Varianten entdeckt worden sind, und das Jahr angegeben. (+) erhöht, ( ) erniedrigt, ka keine Angaben gefunden; GSIS glukosestimulierte Insulinsekre; genomweite Assoziasstudien; SNP single nucleotide polymorphismus ; BMI Body Mass Index.

7 [1] Bonnefond A, Froguel P, Vaxillaire M (2010) The emerging genetics of type 2 diabetes. Trends Mol Med 16: [2] Consortium WTCC (2007) Genome-wide associa study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: [3] Diabetes Genetics Initiative of Broad Institute of Harvard and MIT LU, and Novartis Institutes of Biomedical Research, Saxena R, Voight BF et al (2007) Genome-wide associa analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316: [4] Dina C, Meyre D, Gallina S et al (2007) Varia in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39: [5] Dupuis J, Langenberg C, Prokopenko I et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42: [6] Grant SF, Thorleifsson G, Reynisdottir I et al (2006) Variant of transcrip factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38: [7] Gudmundsson J, Sulem P, Steinthorsdottir V et al (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39: [8] Gupta V, Khadgawat R, Ng HK et al (2010) A valida study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India. Ann Hum Genet 74: [9] Kanoni S, Nettleton JA, Hivert MF et al (2011) Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes 60: [10] Kirchhoff K, Fritsche A, Häring H-U et al (2008) Genetik des Diabetes mellitus Typ 2. Med Welt 59:1 6 [11] Park KS (2011) The search for genetic risk factors of type 2 diabetes mellitus. Diabetes Metab J 35:12 22 [12] Prokopenko I, Langenberg C, Florez JC et al (2009) Variants in MTNR1B influence fasting glucose levels. Nat Genet 41:77 81 [13] Qi L, Cornelis MC, Kraft P et al (2010) Genetic variants at 2q24 are associated with susceptibility to type 2 diabetes. Hum Mol Genet 19: [14] Rung J, Cauchi S, Albrechtsen A et al (2009) Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41: [15] Sandhu MS, Weedon MN, Fawcett KA et al (2007) Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 39: [16] Saxena R, Hivert MF, Langenberg C et al (2010) Genetic varia in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42: [17] Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide associa study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316: [18] Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide associa study identifies novel risk loci for type 2 diabetes. Nature 445: [19] Small KS, Hedman AK, Grundberg E et al (2011) Identifica of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat Genet 43: [20] Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:

8 [21] Strawbridge RJ, Dupuis J, Prokopenko I et al (2011) Genome-wide associa identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 60: [22] Travers ME, McCarthy MI (2011) Type 2 diabetes and obesity: genomics and the clinic. Hum Genet 130:41 58 [23] Tsai FJ, Yang CF, Chen CC et al (2010) A genome-wide associa study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 6:e [24] Unoki H, Takahashi A, Kawaguchi T et al (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populas. Nat Genet 40: [25] Van De Bunt M, Gloyn AL (2010) From genetic associa to molecular mechanism. Curr Diab Rep 10: [26] Voight BF, Scott LJ, Steinthorsdottir V et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale associa analysis. Nat Genet 42: [27] Wheeler E, Barroso I (2011) Genome-wide associa studies and type 2 diabetes. Brief Funct Genomics 10:52 60 [28] Yamauchi T, Hara K, Maeda S et al (2010) A genome-wide associa study in the Japanese popula identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat Genet 42: [29] Yasuda K, Miyake K, Horikawa Y et al (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40: [30] Zeggini E, Scott LJ, Saxena R et al (2008) Meta-analysis of genome-wide associa data and large-scale replica identifies addial susceptibility loci for type 2 diabetes. Nat Genet 40: [31] Zeggini E, Weedon MN, Lindgren CM et al (2007) Replica of genome-wide associa signals in UK samples reveals risk loci for type 2 diabetes. Science 316: