Association between Clozapine-induced Weight Gain and Serotonin 5-HT2C Receptor Gene Polymorphism in Korean Schizophrenic Patients
1
조회
0
다운로드
1
인용
0
참고문헌
초록
Abstract
Weight gain is one of the troublesome adverse reaction to clozapine treatment. This problem can lead to poor adherence to treatment. Clozapine-induced weight gain may be associated with genetic predisposition. Recent studies showed that the polymorphisms of the serotonin 5-HT2C receptor gene is associated with antipsychotic-induced weight gain. This study is to investigate the association of clozapine-induced weight gain with the -759C/T polymorphism of the 5-HT2C receptor gene in Korean schizophrenic patients. The 53 patients were divided into two groups according to the change of body weight between the start and 10 weeks of clozapine treatment. The cutoff level of weight change is 5% increase of initial body weight. Genotypes of the -759C/T polymorphism were identified from Aci I-digested fragments of two-primer products amplified by polymerase chain reaction corresponding to -885 to -634 of the 5-HT2C receptor gene. There were no group differences in basic variables. Four of 32 male and 6 of 21 female patients had the -759T allele, respectively. Clozapine-induced weight gain was significantly less in patients with the -759T allele compared to those without the -759T allele. Weight change tended to be more influenced by the -759T allele in female patients compared to that in male patients, not reaching significance. These findings indicate that the -759C/T polymorphism may be a genetic marker for susceptibility to clozapine-induced weight gain.
참고문헌 (27)
- Allison DB, "Antipsychotic-induced weight gain: A comprehensive research synthesis.", Am J Psychiatry, 156, pp.1686~1696 (1999)
- Ryan MC, "Physical consequences of schizophrenia and its treatment: The metabolic syndrome.", Life Sci, 71, pp.239~257 (2001)
- Zimmermann U, "implications and mechanisms underlying druginduced weight gain in psychiatric patients.", J Psychiatr Res, 37, pp.193~220 (2003)
- Baptista T, "Treatment of the metabolic disturbances caused by antipsychotic drugs: Focus on potential drug interactions.", Clin Pharmacokinet, 43, pp.1~15 (2004)
- Melkersson K, "Adverse metabolic effects associated with atypical antipsychotics: Literature review and clinical implications.", Drugs, 64, pp.701~723 (2004)
- Perkins DO, "Adherence to antipsychotic medications.", J Clin Psychiatry, 60(21), pp.25~30 (1999)
- Henderson DC, "Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study.", Am J Psychiatry, 157, pp.975~981 (2000)
- Leadbetter R, "Clozapine-induced weight gain: Prevalence and clinical relevance.", Am J Psychiatry, 149, pp.68~72 (1992)
- Hong CJ, "Genetic variants of the serotonin system and weight change during clozapine treatment.", Pharmacogenetics, 11, pp.265~268 (2001)
- Wade J, "Evidence for a physiological regulation of food selection and nutrient intake in twins.", Am J Clin Nutr, 34, pp.143~147 (1981)
- Comuzzie AG, "The search for human obesity genes. Science", 280, pp.1374~1378 (1998)
- Casey DE, "The Pharmacology of weight gain with antipsychotics.", J Clin Psychiatry, 62(7), pp.4~10 (2001)
- Tecott LH, "Eating disorder and epilepsy in mice lacking 5-HT sub 2C serotonin receptors.", Nature, 374, pp.542~546 (1995)
- Lappalainen J, "Identification, expression, and pharmacology of a Cys23-Ser23 substitutiom in the human 5-HT2C receptor gene (HTR2C).", Genomics, 27, pp.274~279 (1995)
- Sodhi MS, "Association between clozapine response and allelic variation in the 5-HT2C receptor gene.", Neuroreport, 7, pp.169~172 (1995)
- Lentes KU, "Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: No evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.", Life Sci, 61, pp.9~16 (1997)
- Yuen X, "Identification 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, pp.373~376 (2000)
- Segman RH, "Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: Additive contribution of 5-HT2CSer and DRD3Gly alleles to susceptibility.", Psychopharmacology, 152, pp.408~413 (2000)
- Reynolds GP, "Association of antipsychotic drug-induced weight gain with 5-HT2C receptor gene polymorphism.", Lancet, 359, pp.2086~2087 (2002)
- Reynolds GP, "Polymorphism of the promoter region of the serotonin 5-HT2C receptor gene and clozapine- induced weight gain.", Am J Psychiatry, 60, pp.677~679 (2003)
- Pooley EC, "A 5-HT2C receptor promoter polymorphism (HT-R2C-759C", T) is associated with obesity in women, and with resistance to weight loss in heterozygotes., 2004, pp.126B, 124~127
- Xie E, "The human serotonin 5-HT2C receptor: completel cDNA, genomic structure, and alternatively spliced variant.", Genomics, 35, pp.551~561 (1996)
- Davis J, "A meta-analysis of the efficacy of second-generation antipsychotics.", Arch Gen Psychiatry, 60, pp.553~564 (2003)
- Meltzer HY, "International Suicide Prevention Trial Study Group.", Clozapine treatment for suicidality in schizophrenia: International suicide prevention trial(InterSePT). Arch Gen Psychiatry, 60, pp.82~91 (2003)
- Meltzer HY, "Reducing the risk for suicide in schizophrenia and affective disorders.", J Clin Psychiatry, 64, pp.1122~1129 (2003)
- Hummer M, "Weight gain induced by clozapine.", Eur Neuropsychopharmacol, 437, pp.437~440 (1995)
- Briffa D, "Weight changes during clozapine treatment.", Austr NZJ Psychiatry, 32, pp.718~721 (1998)