Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: An update and meta-analysis

Pharmacogenomics

Volumn 11, Issue 11, 2010, Pages 1561-1571

  Sicard, Michelle N ^a   Zai, Clement C ^a   Tiwari, Arun K ^a   Souza, Renan P ^a   Meltzer, Herbert Y ^b   Lieberman, Jeffrey A ^c   Kennedy, James L ^a   Müller, Daniel J ^a  

^a CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^b Psychiatric Hospital at Vanderbilt   (United States)

^c NEW YORK STATE PSYCHIATRIC INSTITUTE   (United States)

Author keywords

5 HT2C receptor; antipsychotics; genetics; HTR2C; meta analysis; weight gain

Indexed keywords

AMISULPRIDE; CHLORPROMAZINE; CLOZAPINE; FLUPHENAZINE; HALOPERIDOL; ILOPERIDONE; NEUROLEPTIC AGENT; OLANZAPINE; QUETIAPINE; RISPERIDONE; SEROTONIN 2C RECEPTOR; SULPIRIDE; ZIPRASIDONE;

ADULT; ARTICLE; BODY MASS; CONTROLLED STUDY; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DNA POLYMORPHISM; ETHNICITY; FEMALE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; HAPLOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT DURATION; WEIGHT CHANGE; WEIGHT GAIN;

ADULT; ALLELES; ANTIPSYCHOTIC AGENTS; FEMALE; HUMANS; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTOR, SEROTONIN, 5-HT2C; SCHIZOPHRENIA; WEIGHT GAIN;

EID: 78649711976     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.10.123     Document Type: Article

References (59)

1. Tandon R, Jibson MD: Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann. Clin. Psychiatry 14(2), 123-129 (2002).
2. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profles. Mol. Psychiatry 13(1), 27-35 (2008).
3. Yevtushenko OO, Cooper SJ, O'Neill R, Doherty JK, Woodside JV, Reynolds GP: Infuence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br. J. Psychiatry 192(6), 424-428 (2008).
4. De Hert MA, Van Winkel R, Van Eyck D: Prevalence of the metabolic syndrome in patients with schizophrenia treated with antipsychotic medication. Schizophr. Res. 83(1), 87-93 (2006).
5. Haddad PM: Antipsychotics and diabetes: review of non-prospective data. Br. J. Psychiatry 47, S80-S86 (2004).
6. Fontaine KR, Heo M, Harrigan EP et al.: Estimating the consequences of antipsychotic induced weight gain on health and mortality rate. Psychiatry Res. 101(3), 277-288 (2001).
7. Rege S: Antipsychotic-induced weight gain in schizophrenia: mechanisms and management. Aust. NZ J. Psychiatry 42(5), 369-381 (2008).
8. Lieberman JA, Stroup TS, McEvoy JP et al.: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353(12), 1209-1223 (2005).
9. Vickers SP, Easton N, Webster LJ et al.: Oral administration of the 5-HT2C receptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia. Psychopharmacology (Berl.) 167(3), 274-280 (2003).
10. Hayashi A, Suzuki M, Sasamata M, Miyata K: Agonist diversity in 5-HT(2C) receptor-mediated weight control in rats. Psychopharmacology (Berl.) 178(2-3), 241-249 (2005).
11. Clifton PG, Lee MD, Dourish CT: Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist and D-fenfuramine on feeding patterns in the rat. Psychopharmacology (Berl.) 152(3), 256-267 (2000).
12. Simansky KJ: Serotonergic control of the organization of feeding and satiety. Behav. Brain Res. 73(1-2), 37-42 (1996).
13. Bonhaus DW, Weinhardt KK, Taylor M: RS-102221: a novel high affnity and selective, 5-HT2C receptor antagonist. Neuropharmacology 36(4-5), 621-629 (1997).
14. Nonogaki K, Strack AM, Dallman MF, Tecott LH: Leptin-independent hyperphagia and Type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med. 4(10), 1152-1156 (1998).
15. Müller DJ, Kennedy JL: Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics 7(6), 863-887 (2006).
16. Wehmeier PM, Gebhardt S, Schmidtke J, Remschmidt H, Hebebrand J, Theisen FM: Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation. Psychiatry Res. 133(2-3), 273-276 (2005).
17. Theisen FM, Gebhardt S, Haberhausen M: Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs. Psychiatr. Genet. 15(4), 285-289 (2005).
18. Tecott LH, Sun LM, Akana SF: Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374(6522), 542-546 (1995).
19. Akana SF: Feeding and stress interact through the serotonin 2C receptor in developing mice. Physiol. Behav. 94(4), 569-579 (2008).
20. Jibson MD, Tandon R: New atypical antipsychotic medications. J. Psychiatr. Res. 32(3-4), 215-228 (1998).
21. Allison DB, Mentore JL, Heo M: Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156(11), 1686-1696 (1999).
22. Reynolds GP, Hill MJ, Kirk SL: The 5-HT2C receptor and antipsychotic-induced weight gain - mechanisms and genetics. J. Psychopharmacol. 20(4S), 15-18 (2006).
23. Hannon J, Hoyer D: Molecular biology of 5-HT receptors. Behav. Brain Res. 195(1), 198-213 (2008).
24. Yuan XM, Zhou YT, Zhang HY, Xue H, Zhou L, Zhao Y: Identifcation of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and Type II diabetes. Diabetologia 43(3), 373-376 (2000).
25. Reynolds GP, Zhang ZJ, Zhang XB: Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 359(9323), 2086-2087 (2002).
26. Ellingrod VL, Perry PJ, Ringold JC: Weight gain associated with the -759C/T polymorphism of the 5HT2C receptor and olanzapine. Am. J. Med. Genet. B Neuropsychiatr. Genet. 134B(1), 76-78 (2005).
27. Ryu S, Huppmann AR, Sambangi N, Takacs P, Kauma SW: -759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. Prog. Neuropsychopharmacol. Biol. Psychiatry 31(3), 673-677 (2007).
28. Godlewska BR, Olajossy-Hilkesberger L, Ciwoniuk M et al.: Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene. Pharmacogenomics J. 9(4), 234-241 (2009).
29. Gunes A, Melkersson KI, Scordo MG, Dahl ML: Association between a 5HT2C receptor haplotype and metabolic abnormalities in patients treated with olanzapine. Eur. Neuropsychopharmacol. 17, S452-S453 (2007).
30. 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 frst-episode psychosis. Pharmacogenet. Genomics. 15(4), 195-200 (2005).
31. Miller DD, Ellingrod VL, Holman TL, Buckley PF, Arndt S: Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism. Am. J. Med. Genet. B Neuropsychiatr. Genet. 133B(1), 97-100 (2005).
32. 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 160(4), 677-679 (2003).
33. Tsai SJ, Hong CJ, Yu YW, Lin CH: -759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 360(9347), 1790 (2002).
34. Basile VS, Masellis M, De Luca V, Meltzer HY, Kennedy JL: -759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 360(9347), 1790-1791 (2002).
35. De Luca V, Müller DJ, Hwang R et al.: HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker ana lysis. Hum. Psychopharmacol. 22(7), 463-467 (2007).
36. Hong CJ, Lin CH, Yu YW, Yang KH, Tsai SJ: Genetic variants of the serotonin system and weight change during clozapine treatment. Pharmacogenetics 11(3), 265-268 (2001).
37. Ujike H, Nomura A, Morita Y: Multiple genetic factors in olanzapine-induced weight gain in schizophrenia patients: a cohort study. J. Clin. Psychiatry 69(9), 1416-1422 (2008).
38. Rietschel M, Naber D, Fimmers R, Möller HJ, Propping P, Nöthen MM: Effcacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor. Neuroreport 8, 1999-2003 (1997).
39. 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 62(Suppl. 23), 45-66 (2001).
40. Popp J, Leucht S, Heres S, Steimer W: DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain. Pharmacogenomics J. 9(1), 71-77 (2009).
41. Hill MJ, Reynolds GP: 5-HT2C receptor gene polymorphisms associated with antipsychotic drug action alter promoter activity. Brain Res. 1149, 14-17 (2007).
42. Lahiri DK, Nurnberger JI: A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 19, 5444 (1991).
43. Dudbridge F: Pedigree disequilibrium tests for multilocus haplotypes. Genet. Epidemiol. 25(2), 115-121 (2003).
44. Barrett JC, Fry B, Maller J, Daly MJ: Haploview: ana lysis and visualization of LD and haplotype maps. Bioinformatics 21(2), 263-265 (2005).
45. De Luca V, Müller DJ, de Bartolomeis A, Kennedy JL: Association of the HTR2C gene and antipsychotic-induced weight gain: a meta-ana lysis. Int. J. Neuropsychopharmacol 9, 169-177 (2007).
46. Der Simonian R, Laird N: Meta-ana lysis in clinical trials. Controlled Clin. Trials 7, 177-188 (1986).
47. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-ana lysis detected by a simple, graphical test. Br. Med. J. 315, 629-634 (1997).
48. Girgis RR, Javitch JA, Lieberman JA: Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway. Mol. Psychiatry 13(10), 918-929 (2008).
49. Krakowski M, Czobor P, Citrome L: Weight gain, metabolic parameters, and the impact of race in aggressive inpatients randomized to double-blind clozapine, olanzapine or haloperidol. Schizophr. Res. 110(1-3), 95-102 (2009).
50. Zipursky RB, Gu H, Green AI et al.: Course and predictors of weight gain in people with frst-episode psychosis treated with olanzapine or haloperidol. Br. J. Psychiatry 187, 537-543 (2005).
51. Buckland PR, Hoogendoorn B, Guy CA, Smith SK, Coleman SL, O'DonoVan MC: Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain. Am. J. Psychiatry 162(3), 613-615 (2005).
52. Okada M, Northup JK, Ozaki N, Russell JT, Linnoila M, Goldman D: Modifcation of human 5-HT(2C) receptor function by Cys23Ser, an abundant, naturally occurring amino-acid substitution. Mol. Psychiatry 9(1), 55-64 (2004).
53. Müller DJ, Muglia P, Fortune T, Kennedy JL: Pharmacogenetics of antipsychotic-induced weight gain. Pharmacol. Res. 49(4), 309-329 (2004).
54. Reynolds GP, Kirk SL: Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol. Ther. 125(1), 169-179 (2010).
55. Gregoor JG, Van der Weide J, Mulder H et al.: Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication. J. Clin. Psychopharmacol. 29(1), 21-25 (2009).
56. Tiwari AK, Zai CC, Likhodi O et al.: A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in schizophrenia. Neuropsychopharmacology 35(6), 1315-1324 (2010).
57. Thompson A, Lavedan C, Volpi S: Absence of weight gain association with the HTR2C -759C/T polymorphism in patients with schizophrenia treated with iloperidone. Psychiatry Res. 175(3), 271-273 (2010).
58. Park YM, Chung YC, Lee SH et al.: Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. J. Clin. Pharm. Ther. 33(1), 55-60 (2008).
59. Theisen FM, Hinney A, Brömel T 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. Psychiatr. Genet. 14(3), 139-142 (2004).