GABRB2基因rs194072和rs187269位点遗传多态性与首发精神分裂症及利培酮疗效的关联性研究

Association between polymorphisms of rs194072,rs187269 in GABRB2 gene and first-episode schizophrenia and the efficacy of risperidone

目的探讨γ-氨基丁酸β2受体(GABRB2)基因多态性与首发精神分裂症及其利培酮疗效的相关性。方法采用SYBR Green I荧光等位基因特异性实时PCR基因分型法完成277例精神分裂症患者(研究组)和315例正常对照者(对照组)的GABRB2基因rs194072和rs187269两个位点多态性的测定。研究组采用利培酮治疗8周,于治疗前及治疗后第8周末用阳性和阴性综合征量表(PANSS)评估疗效。结果两组rs194072(T/C)和rs187269(T/C)位点的基因型与等位基因频率比较,差异有统计学意义(P<0.05)。研究组CC单倍型频率高于对照组(P=0.003),TT单倍型频率低于对照组(P=0.004)。rs187269位点利培酮治疗有效组与无效组在基因型(P=0.003)与等位基因(P=0.004)频率的差异有统计学意义。结论 GABRB2基因rs194072和rs187269多态性可能与首发精神分裂症有关联,rs187269与利培酮片治疗的个体化差异有关联。

Objective To explore the association between polymorphisms of Gamma-aminobutyric acid receptor subunit beta-2 （GABRB2 ） gene and first-episode schizophrenia,as well as the association with efficacy of risperidone.Methods Polymorphisms of rs194072 and rs187269 in GABRB2 gene was genotyped by using a SYBR Green based real time PCR assay in 277 schizophrenic patients （study group）and 315 healthy controls （control group）.Patients in study group were treated with risperidone for 8 weeks and were assessed with Positive and negative Syndrome Scale （PANSS）at baseline and at the end of the treatment.Results There were significant differences in genotypic frequency and allelic frequency of rs194072 （χ2 =7.93,8.64 respectively;P =0.02,0.003 respectively）and rs187269 （χ2 =9.79,8.23 respectively;P =0.008,0.004 respectively） between study group and control group.The haplotype frequency of CC in study group was significantly higher than that in control group （P =0.003）and the haplotype frequency of TT in study group was significantly lower than that in control group （P =0.004）.There were significant differences in distribution of genotypes and alleles of rs187269 between patients response to risperidone and patients invalid to risperidone （P =0.003,0.004 respectively）.Conclusion The polymorphisms of rs194072 and rs187269 in GABRB2 gene are likely associated with the pathogenesis of schizophrenia and polymorphism of rs187269 is likely associated with the efficacy of risperidone.