[Association of antipsychotic agent-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene].
OBJECTIVE
To determine whether 5-hydroxytryptamine 2C (5-HT2C) receptor gene 759C/T polymorphism influences the weight gain following antipsychotic agents (APS) treatment in patient with schizophrenia.


METHODS
DNA was extracted from the peripheral blood of 117 Chinese first-episode patients of Han nationality with schizophrenia diagnosed according to CCMD-II-R criteria. PCR-RELP technique was used to analyse the frequencies of 5-HTR2C receptor gene 759C/T hemizygote (male) and genotype (female). Monotherapy with APS (chlorpromazine or rispperidone) was given for 10 weeks. The body weight was taken and body mass index (BMI) was calculated on admission and every week subsequently for each patient. The correlation of hemizygote or genotype and the BMI was analyzed.


RESULTS
Ten weeks after treatment, there was an average increase in body weight of (3.2 +/- 3.5) kg or (5.7 +/- 6.2)% of the baseline weight with a range of -7 kg approximately 12 kg or -7.8% approximately 32%. The frequency of mutant hemizygote was 58% among the 58 male subjects; the frequency of mutant homozygote was 0%, and the frequency of mutant heterozygote was 27.0% among the 59 female subjects. The body weight gain > 7% occurred in 53% of wild type hemizygote males and 47% of wild type homozygote females; and only 18% of mutant hemizygote males and 13% of mutant heterozygote females. The proportions of 759T hemizygote males or heterozygote females in those with body weight gain > 7% and those with body weight < 7% were significantly different (chi(2) = 22.35, v1, P = 0.000 1; chi(2) = 12.36, v1, P = 0.000 1). Patients without mutant allele were five to six times more likely to develop substantial weight gain (OR = 5.11, 6.68).


CONCLUSIONS
The 5-HT2C-receptor gene -759C/T polymorphism is associated with APS-induced weight gain. 759C-->T may be a protective factor for the development of weight gain in Chinese schizophrenic patients of Han nationality.
Zhang
Zhijun
Z
Psychiatry Department and Clinical Science Center, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China.
Zhang
Xiaobin
X
Yao
Zhijian
Z
Chen
Jianfang
J
Sun
Jing
J
Yao
Hui
H
Hou
Gang
G
Zhang
Xinbao
X
Reynolds
Gavin P
GP
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D004247:DNA