Genetic association between TNF-alpha -308 G>A polymorphism and longitudinal weight change during clozapine treatment.
OBJECTIVE
The aim of the study was to investigate the association between genetic variation in the tumor necrosis factor-alpha (TNF-alpha) gene and longitudinal weight change during long-term clozapine treatment.


METHODS
Fifty-five patients with refractory schizophrenia treated with clozapine for 8 years were recruited. Gender, age, treatment response to clozapine in the first 14 months, baseline BMI, clozapine dose, concomitant use of mood stabilizers and other antipsychotics, and -308 G > A polymorphism in the human TNF-alpha gene were analyzed using generalized estimating equations.


RESULTS
In addition to having a lower baseline BMI (p = 0.0013) and a longer treatment time (p = 0.050), the -308 GG carriers gained significantly more weight than the -308 A allele carriers (p = 0.0084) during 8 years of clozapine treatment, after controlling for other non-genetic factors.


CONCLUSIONS
The -308 G > A genetic variant of the TNF-alpha gene is associated with longitudinal weight change during clozapine treatment. Follow-up duration is an important factor to consider when performing pharmacogenetic study of clozapine-induced weight gain.
Wang
Ying-Chieh
YC
Department of Psychiatry, Yuli Veterans Hospital, Yuli, Hualien, Taiwan, ROC.
Bai
Ya-Mei
YM
Chen
Jen-Yeu
JY
Lin
Chao-Cheng
CC
Lai
I-Ching
IC
Liou
Ying-Jay
YJ
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
D014150:Antipsychotic Agents; D014409:Tumor Necrosis Factor-alpha; D003024:Clozapine