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.