Association of the α2A adrenergic receptor -1291C/G polymorphism and antipsychotic-induced weight gain in European-Americans

Aims: To investigate the -1291 C/G promoter polymorphism (rs1800544) of the adrenergic α-2A receptor (ADRA2A) with clozapine-/olanzapine-induced weight gain in European-Americans and African-Americans. The α-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. Materials & methods: 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. Results: 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. Conclusion: Our observations suggest a possible role of ADRA2A polymorphisms in clozapine- /olanzpaine-induced weight gain in subjects of European descent.