Zhang Zhi-jun, Yao Zhi-jian, Mou Xiao-dong, Chen Jian-fang, Zhu Rong-xin, Liu Wen, Zhang Xiang-rong, Sun Jing, Hou Gang
Department of Psychiatry and Clinical Science Center, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China.
Zhonghua Yi Xue Za Zhi. 2003 Dec 25;83(24):2119-23.
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.
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).
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).
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.
研究瘦素基因启动子区域-2548G/A功能多态性是否影响精神分裂症患者抗精神病药物（APS）急性治疗后的体重增加。
招募128例未接受过治疗的中国汉族精神分裂症患者（男性61例，女性67例），并选取年龄和性别匹配的健康对照者38例。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测瘦素基因的多态性。对22例对照者和30例患者在入院时及使用利培酮或氯丙嗪治疗10周后进行磁共振成像（MRI）测定腹部体脂。对患者在入院时及随后每周测量体重指数（BMI）。
治疗10周后，体重较基线平均增加（6.2±5.7）%，腹部皮下脂肪（SUB）较基线平均增加（38.5±42）%，腹内脂肪（IAF）较基线平均增加（40.0±41.2）%。患者与对照者之间以及不同性别组之间的等位基因和基因型分布均无显著差异。发现-2548AA基因型患者体重增加显著（χ² = 7.529，自由度 = 1，P = 0.006；比值比 = 1.941；95%可信区间：1.175 - 3.207）；基因型对患者和对照者的基线体重指标均无影响。然而，与携带G等位基因的患者相比，AA基因型患者的BMI（P = 0.003）和SUB（P = 0.009）显著增加。
研究结果表明瘦素基因启动子区域的-2548G/A多态性与APS诱导的体重增加以及腹部脂肪沉积和分布有关。-2548AA可能是中国汉族精神分裂症患者在APS急性治疗期间体重增加和体脂沉积的遗传危险因素。
