Gu Bo, Wang Lei, Zhang Ai-Ping, Ma Gang, Zhao Xin-Zhi, Li Hua-Fang, Feng Guo-Ying, He Lin, Xing Qing-He
Bio-X Center, Shanghai Jiao Tong University, Fudan University, Shanghai, China.
Pharmacogenet Genomics. 2008 Aug;18(8):721-7. doi: 10.1097/FPC.0b013e32830500e2.
Certain components of the serotonin system have been known for some time to be risk factors for schizophrenia. Few studies have, however, focused on the association between the therapeutic responses to atypical antipsychotics, such as risperidone, and polymorphisms of the 5-HT3 receptor, the only ionotropic ligand-gated serotonin receptor, even though there have been some genetic clues linking HTR3A and schizophrenia. We therefore postulated that such a polymorphism might be an explanatory factor in the diversity of response to risperidone treatment.
The study recruited 107 drug-naive Chinese schizophrenia patients who were given 8 weeks of risperidone monotherapy and it explored three of four single nucleotide polymorphisms spanning HTR3A for possible association with therapeutic improvement, using the Positive and Negative Symptom Scale.
Significant correlation between the baseline score and therapeutic improvement was observed in each subscale (P<0.001). Statistical analysis revealed association between genotypes of g.14396A>G polymorphism (rs1176713) and score reductions of negative and general subscales after adjusting for the influence of the baseline scores of each subscale [P (F, d.f.)=0.026 (3.763, 2), 0.023 (3.937, 2) respectively]. One haplotype, C-A-G, contributed to an effective response in general symptoms (chi(2)=7.3, P=0.007, odds ratio=3.371).
The results of this study are the first to suggest that the polymorphism of HTR3A may be a useful predictor of therapeutic response to risperidone treatment in Chinese schizophrenic patients, although these conclusions should be treated with caution because of the intricacy of the variety of the therapeutic effects to risperidone.
一段时间以来，人们已经知道血清素系统的某些成分是精神分裂症的危险因素。然而，尽管有一些基因线索将HTR3A与精神分裂症联系起来，但很少有研究关注非典型抗精神病药物（如利培酮）的治疗反应与5-HT3受体（唯一的离子型配体门控血清素受体）多态性之间的关联。因此，我们推测这种多态性可能是利培酮治疗反应多样性的一个解释因素。
该研究招募了107名未服用过药物的中国精神分裂症患者，给予他们8周的利培酮单一疗法，并使用阳性和阴性症状量表，探索了跨越HTR3A的四个单核苷酸多态性中的三个与治疗改善之间的可能关联。
在每个子量表中均观察到基线评分与治疗改善之间存在显著相关性（P<0.001）。统计分析显示，在调整每个子量表基线评分的影响后，g.14396A>G多态性（rs1176713）的基因型与阴性和一般子量表的评分降低之间存在关联[P（F，自由度）分别为0.026（3.763，2），0.023（3.937，2）]。一种单倍型C-A-G对一般症状的有效反应有贡献（卡方=7.3，P=0.007，优势比=3.371）。
本研究结果首次表明，HTR3A的多态性可能是中国精神分裂症患者对利培酮治疗反应的有用预测指标，尽管由于利培酮治疗效果的复杂性，这些结论应谨慎对待。
