Popp J, Leucht S, Heres S, Steimer W
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Pharmacogenomics J. 2009 Feb;9(1):71-7. doi: 10.1038/tpj.2008.5. Epub 2008 Mar 11.
Weight gain is a major side effect of antipsychotic treatment. The antidopaminergic and antiserotonergic effect of antipsychotics may contribute to antipsychotic-induced weight gain. We, therefore conducted a prospective clinical study, to investigate whether the D4 receptor (DRD4) 48 bp (base pair) variable number of tandem repeat (VNTR) polymorphism and the 5-hydroxytryptamine 2C receptor (HT(2C)) cysteine for serine substitution at position 23 (Cys23Ser) polymorphism may influence weight gain during antipsychotic treatment in a naturalistic setting of 102 Caucasian psychiatric in-patients. Patients suffering from psychotic disorders and treated according to local clinical practice were classified as either homozygous for the shorter alleles of the DRD4 48 bp VNTR polymorphism (<7-fold repeat, group 1) or heterozygous/homozygous for the long allele (7-fold repeat or higher, group 2). HT(2C) Cys23Ser polymorphism male patients were grouped hemizygous G (Cys) or C (Ser), while female patients were GG, GC or CC and both sexes were evaluated separately. Concerning the DRD4 48 bp VNTR polymorphism the increase in body mass index was significantly less in group 1 (0.38 kg m(-2); s.d.=1.04) than in group 2 (0.89 kg m(-2); s.d.=1.23; P=0.003). The difference between the genotype groups remained significant in male patients but not in female patients. In contrast, no influence on antipsychotic-induced increase in body weight was observed for the HT(2C) Cys23Ser polymorphism. These results support the hypothesis that the DRD4 48 bp VNTR polymorphism influences antipsychotic-induced weight gain. Male patients may be more affected than female patients. Due to the limitations of the study (heterogeneity of treatment, pretreatment and concomitant therapy) further studies are required before diagnostic genotyping of the DRD4 48 bp VNTR polymorphism may be useful for individualizing therapy.
体重增加是抗精神病药物治疗的一个主要副作用。抗精神病药物的抗多巴胺能和抗5-羟色胺能作用可能导致抗精神病药物引起的体重增加。因此，我们进行了一项前瞻性临床研究，以调查102名白种人精神科住院患者在自然环境下接受抗精神病药物治疗期间，D4受体（DRD4）48碱基对（bp）可变串联重复序列（VNTR）多态性以及5-羟色胺2C受体（HT（2C））第23位半胱氨酸到丝氨酸替代（Cys23Ser）多态性是否会影响体重增加。患有精神疾病并按照当地临床实践进行治疗的患者被分为DRD4 48 bp VNTR多态性短等位基因纯合子（<7次重复，第1组）或长等位基因杂合子/纯合子（7次重复或更高，第2组）。HT（2C）Cys23Ser多态性男性患者分为半合子G（Cys）或C（Ser），女性患者分为GG、GC或CC，且对男女患者分别进行评估。关于DRD4 48 bp VNTR多态性，第1组的体重指数增加（0.38 kg m-2；标准差=1.04）明显低于第2组（0.89 kg m-2；标准差=1.23；P=0.003）。基因型组之间的差异在男性患者中仍然显著，但在女性患者中不显著。相比之下，未观察到HT（2C）Cys23Ser多态性对抗精神病药物引起的体重增加有影响。这些结果支持DRD4 48 bp VNTR多态性影响抗精神病药物引起的体重增加这一假设。男性患者可能比女性患者受影响更大。由于该研究的局限性（治疗、预处理和伴随治疗的异质性），在DRD4 48 bp VNTR多态性的诊断基因分型可能有助于个体化治疗之前，还需要进一步研究。
