瘦素基因启动子区-2548G/A功能多态性与抗精神病药源性肥胖的相关分析

目的　探讨瘦素基因启动子区 - 2 5 4 8G/A功能多态性是否与首次治疗精神分裂症患者的抗精神病药物 (APS)急性期治疗导致的体重增加相关。方法　采用聚合酶链反应 限制片段长度多态性 (PCR RFLP)技术分析 12 8例患者 (男 6 1例 ,女 6 7例 ) - 2 5 4 8G/A等位基因和基因型分布频率 ,APS(利培酮或氯丙嗪 )单药治疗 10周 ,治疗前后每周测体重和体重指数 (BMI) ,采用MRI测治疗前后腹部脂肪分布 (30例 ) ,分析等位基因和基因型与基础体重指标和其变化值的相关性 ;同时分析 38名性别、年龄和BMI相匹配的健康对照者 ,其中 2 2例进行MRI扫描。结果　治疗后患者体重增加是基础体重的 (6 .2± 5 .7) % ,腹部脂肪增加是基础腹部皮下脂肪 (SUB)的 (38.5± 4 2 ) %、腹内脂肪的 (4 0 .0± 4 1.2 ) % ;- 2 5 4 8G/A等位基因和基因型在患者组和对照组分布频率差异无显著意义 ;在体重增加≤ 7%和 >7%患者组等位基因和基因型分布频率差异有非常显著意义 (χ2 =7 5 2 9,df =1,P =0 .0 0 6 ;OR =1.94 1;95 %CI:1.175～ 3.2 0 7) ;基因型对患者组或对照组的基础体重指标无显著影响 ;与携带G等位基因患者相比 ,AA基因型携带者治疗后BMI(P =0 .0 0 3)和SUB(P =0 .0 0 9)明显增加。结论　瘦素基因启动子区 - 2 5 4 8G/A功能多态

Association of -2548G/A functional polymorphism in the promoter region of leptin gene with antipsychotic agent-induced weight gain

OBJECTIVE: To investigate whether the -2548G/A functional polymorphism in promoter region of leptin gene influencing weight gain following antipsychotic agents (APS) acute treatment in schizophrenic patients. METHODS: 128 Chinese Han untreated patients with schizophrenia (male 61, female 67) with an age and gender matched health controls (n = 38) were recruited. The polymorphism of leptin gene was determined with PCR-RFLP technique. MRI determined abdominal body fat in 22 controls and 30 patients on admission and after 10 weeks treatment with risperidone or chlorpromazine. Body mass index (BMI) was measured on admission and every week subsequently (for patients). RESULTS: There were average increases in (6.2 +/- 5.7)% of baseline weight and in (38.5 +/- 42)% of baseline abdominal subcutaneous fat (SUB) and in (40.0 +/- 41.2)% of baseline intra-abdominal fat (IAF) 10 weeks after treatment. There were no significant differences in the distribution of allele and genotypes either between the patients and controls or between gender groups. It was found significantly increased weight gain in the patient with the -2548AA genotype (chi(2) = 7.529, df = 1, P = 0.006; OR = 1.941; 95% CI: 1.175 - 3.207); The genotypes had no influence on the baseline weight indicators both in patients and controls. However, as compared with the patients with G allele, the patients with AA genotype had significant increase in BMI (P = 0.003) and SUB (P = 0.009). CONCLUSION: The finding identify that the -2548G/A polymorphism in promoter region of leptin gene associated with APS-induced weight gain and abdominal fat deposition and distribution. -2548AA may be a genetic risk factor for the development of weight gain and body fat deposition in Chinese Han schizophrenic patients during APS acute treatment.