Genetic association between TNF-α −308 G>A polymorphism and longitudinal weight change during clozapine treatment

✍ Scribed by Ying-Chieh Wang; Ya-Mei Bai; Jen-Yeu Chen; Chao-Cheng Lin; I-Ching Lai; Ying-Jay Liou

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 105 KB
• Volume: 25
• Category: Article
• ISSN: 0885-6222
• DOI: 10.1002/hup.1122

✦ Synopsis

Abstract

Objective

The aim of the study was to investigate the association between genetic variation in the tumor necrosis factor‐alpha (TNF‐α) 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‐α 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‐α 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. Copyright © 2010 John Wiley & Sons, Ltd.