Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: Perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects?

Molecular Psychiatry

Volumn 14, Issue 3, 2009, Pages 308-317

  Le Hellard, S ^a,b   Theisen, F M ^c   Haberhausen, M ^c   Raeder, M B ^a,b   Ferno J ^a,b   Gebhardt, S ^c   Hinney, A ^d   Remschmidt, H ^c   Krieg, J C ^c   Mehler Wex, C ^e   Nothen M M ^f   Hebebrand, J ^d   Steen, V M ^a,b  

^a HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF BERGEN   (Norway)

^c PHILIPPS UNIVERSITY MARBURG   (Germany)

^d UNIVERSITY OF DUISBURG ESSEN   (Germany)

^e UNIVERSITY OF ULM   (Germany)

^f UNIVERSITY OF BONN   (Germany)

Author keywords

Antipsychotic; Cholesterol; Functional convergent genomics; Gene; Metabolic syndrome

Indexed keywords

ATYPICAL ANTIPSYCHOTIC AGENT; CLOZAPINE; STEROL REGULATORY ELEMENT BINDING PROTEIN;

ADULT; ARTICLE; BODY MASS; CHOLESTEROL SYNTHESIS; DYSLIPIDEMIA; ENERGY EXPENDITURE; FATTY ACID SYNTHESIS; FEMALE; FOOD INTAKE; GENE; GENE EXPRESSION; GENOTYPE; GERMANY; HUMAN; HYPOTHALAMUS; INSIG1 GENE; INSIG2 GENE; LIPOGENESIS; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PRIORITY JOURNAL; PSYCHOSIS; SCAP GENE; SCHIZOPHRENIA; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; SREBF1 GENE; SREBF2 GENE; WEIGHT GAIN;

ADOLESCENT; ADULT; ANTIPSYCHOTIC AGENTS; CHI-SQUARE DISTRIBUTION; CHILD; CLOZAPINE; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HAPLOTYPES; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LINKAGE (GENETICS); LIPOGENESIS; MALE; MEMBRANE PROTEINS; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RETROSPECTIVE STUDIES; SCHIZOPHRENIA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; STEROL REGULATORY ELEMENT BINDING PROTEINS; WEIGHT GAIN; YOUNG ADULT;

EID: 60549089825     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/sj.mp.4002133     Document Type: Article

References (52)

1. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686-1696.
2. Lindenmayer JP, Czobor P, Volavka J, Citrome L, Sheitman B, McEvoy JP et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003; 160: 290-296.
3. Meyer JM, Koro CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res 2004; 70: 1-17.
4. Saari KM, Lindeman SM, Viilo KM, Isohanni MK, Järvelin MR, Laurén LH et al. A 4-fold risk of metabolic syndrome in patients with schizophrenia: the Northern Finland 1966 Birth Cohort study. J Clin Psychiatry 2005; 66: 559-563.
5. Lamberti JS, Olson D, Crilly JF, Olivares T, Williams GC, Tu X et al. Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry 2006; 163: 1273-1276.
6. Marder SR, Essock SM, Miller AL, Buchanan RW, Casey DE, Davis JM et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1334-1349.
7. Osborn DP, Levy G, Nazareth I, Petersen I, Islam A, King MB. Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom's General Practice Research Database. Arch Gen Psychiatry 2007; 64: 242-249.
8. Arranz MJ, de Leon J. Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry 2007; 12: 707-747.
9. Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P et al. H1-histamine receptor affinity predicts shortterm weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 2003; 28: 519-526.
10. Matsui-Sakata A, Ohtani H, Sawada Y. Receptor occupancy-based analysis of the contributions of various receptors to antipsychotics-induced weight gain and diabetes mellitus. Drug Metab Pharmacokinet 2005; 20: 368-378.
11. Kim SF, Huang AS, Snowman AM, Teuscher C, Snyder SH. Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci 2007; 104: 3456-3459.
12. Basile VS, Masellis M, McIntyre RS, Meltzer HY, Lieberman JA, Kennedy JL. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry 2001; 62: 45-66.
13. Theisen FM, Gebhardt S, HaberhausenM, Heinzel-GutenbrunnerM, Wehmeier PM, Krieg JC et al. Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs. Psychiatry Genet 2005; 15: 285-289.
14. Müller DJ, Kennedy JL. Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics 2006; 7: 863-887.
15. Chagnon YC. Susceptibility genes for the side effect of antipsychotics on body weight and obesity. Curr Drug Targets 2006; 7: 1681-1695.
16. Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002; 359: 2086-2087.
17. Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry 2003; 160: 677-679.
18. Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet 2005; 15: 195-200.
19. Lane HY, Lin CC, Huang CH, Chang YC, Hsu SK, Chang WH. Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders. Schizophr Res 2004; 67: 63-70.
20. Ryu S, Cho EY, Park T, Oh S, Jang WS, Kim SK et al. 759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 673-677.
21. Theisen FM, Hinney A, Bromel T, Heinzel-Gutenbrunner M, Martin M, Krieg JC et al. Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatry Genet 2004; 14: 139-142.
22. Ferno J, Raeder MB, Vik-Mo AO, Skrede S, Glambek M, Tronstad KJ et al. Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action? Pharmacogenomics 2005; 5: 298-304.
23. Raeder MB, Ferno J, Glambek M, Stansberg C, Steen VM. Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neuroscience Let 2006; 395: 185-190.
24. Ferno J, Skrede S, Vik-Mo AO, Håvik B, Steen VM. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs. BMC Neurosci 2006; 7: p 69.
25. Dietschy JM, Turley SD. Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 2004; 45: 1375-1397.
26. Edwards PA, Tabor D, Kast HR, Venkateswaran A. Regulation of gene expression by SREBP and SCAP. Biochim Biophys Acta 2000; 1529: 103-113.
27. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002; 109: 1125-1131.
28. Nakamura MT, Cheon Y, Li Y, Nara TY. Mechanisms of regulation of gene expression by fatty acids. Lipids 2004; 39: 1077-1083.
29. Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 2002; 110: 489-500.
30. Rawson RB. Control of lipid metabolism by regulated intramembrane proteolysis of sterol regulatory element binding proteins (SREBPs). Biochem Soc Symp 2003; 70: 221.
31. Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS, Goldstein JL. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest 1997; 99: 846-854.
32. Horton JD, Shimomura I, Brown MS, Hammer RE, Goldstein JL, Shimano H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. J Clin Invest 1998; 101: 2331-2339.
33. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest 1996; 98: 1575-1584.
34. Eberlé D, Clément K, Meyre D, Sahbatou M, Vaxillaire M, Le Gall A et al. SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts. Diabtes 2004; 53: 2153-2157.
35. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T et al. A common genetic variant is associated with adult and childhood obesity. Science 2006; 312: 279-283.
36. Lyon HN, Emilsson V, Hinney A, Heid IM, Lasky-Su J, Zhu X et al. The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts. PLoS Genet 2007; 3: e61.
37. Bromel T, Blum WF, Ziegler A, Schulz E, Bender M, Fleischhaker C et al. Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiatry 1998; 3: 76-80.
38. Theisen FM, Linden A, Geller F, Schafer H, Martin M, Remschmidt H et al. Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication. J Psychiatr Res 2001; 35: 339-345.
39. Gordon D. Viewing and Editing Assembled Sequences Using Consed. Current Protocols in Bioinformatics, In: Baxevanis AD, Davison DB (eds). Current Protocols in Bioinformatics. John Wiley: New York, 2004, pp 11.12.11-11.12.43.
40. Nyholt DR. A simple correction for multiple testing for SNPs in linkage disequilibrium with each other. Am J Hum Genet 2004; 74: 765-769.
41. Dina C, Meyre D, Samson C, Tichet J, Marre M, Jouret B et al. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007; 315: 187.
42. Loos RJ, Barroso I, O'rahilly S, Wareham NJ. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007; 315: 187.
43. Rosskopf D, Bornhorst A, Rimmbach C, Schwahn C, Kayser A, Kruger A et al. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007; 315: 187.
44. Hall DH, Rahman T, Avery PJ, Keavney B. INSIG-2 promoter polymorphism and obesity related phenotypes: association study in 1428 members of 248 families. BMC Med Genet 2007; 30: 83.
45. Kumar J, Sunkishala RR, Karthikeyan G, Sengupta S. The common genetic variant upstream of INSIG2 gene is not associated with obesity in Indian population. Clin Genet 2007; 71: 415-418.
46. Smith AJ, Cooper JA, Li LK, Humphries SE. INSIG2 gene polymorphism is not associated with obesity in Caucasian, Afro-Caribbean and Indian subjects. Int J Obes 2007; 31: 1753-1755.
47. Feng Y, Dong H, Xiang Q, Hong X, Wilker E, Zhang Y et al. Lack of association between rs7566605 and obesity in a Chinese population. Hum Genet 2007; 120: 743-745.
48. Skelly T, Pinheiro AP, Lange LA, Sullivan PF. Is rs7566605, a SNP near INSIG2, associated with body mass in a randomized clinical trial of antipsychotics in schizophrenia? Mol Psychiatry 2007; 12: 321-322.
49. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209-1223.
50. Cervino AC, Li G, Edwards S, Zhu J, Laurie C, Tokiwa G et al. Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels. Genomics 2005; 86: 505-517.
51. Yabe D, Komuro R, Liang G, Goldstein JL, Brown MS. Liver-specific mRNA for Insig-2 down-regulated by insulin: implications for fatty acid synthesis. Proc Natl Acad Sci 2003; 100: 3155-3160.
52. Bai YM, Lin CC, Chen JY, Lin CY, Su TP, Chou P. Association of initial antipsychotic response to clozapine and long-term weight gain. Am J Psychiatry 2006; 163: 1276-1279.