Abstract
To investigate the -1291 C/G promoter polymorphism (rs1800544) of the adrenergic alpha-2A receptor (ADRA2A) with clozapine-/olanzapine-induced weight gain in European-Americans and African-Americans. The alpha-adrenergic receptors inhibit lipolysis in the adipose tissue and are involved in weight gain regulation. Moreover, two previous studies indicated an association with antipsychotic-induced weight gain with the same polymorphism in Asian populations. We analyzed a relatively large (n=129) and well-characterized group of patients and monitored them for a period of 6-14 weeks. Our refined sample consisted of 60 European-Americans and 39 African-Americans on clozapine or olanzapine, prospectively. In European-Americans, we observed a significant difference in weight gain across the genotypic categories (p=0.046). The carriers of the C allele gained more weight compared with the subjects homozygous for the GG allele (CC + CG vs GG; 3.73 +/- 4.13 kg vs 0.23 +/- 2.92 kg; p=0.013). We did not find a significant association in African-Americans, although the sample size was probably too small. Our observations suggest a possible role of ADRA2A polymorphisms in clozapine-/olanzpaine-induced weight gain in subjects of European descent.
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