HTR1A基因-1019C/G多态性与重性抑郁障碍及氟西汀疗效的关联研究

Relationship between HTR1A Gene-1019C/G Polymorphism and Clinical Response of Fluoxetine in the Treatment of Major Depressive Disorder

目的探讨5羟色胺1A受体(HTR1A)基因多态性与重性抑郁障碍的相关性及与氟西汀治疗疗效之间的关系。方法采用聚合酶链式反应扩增技术与限制性片段长度多态性分析技术(PCR-RFLP)检测重性抑郁障碍患者(病例组,n=142)和正常人(对照组,n=154)HTR1A基因-1019C/G多态性的基因型和等位基因频率。氟西汀治疗前及治疗6周末,用17项汉密尔顿抑郁量表(HAMD)评价疾病严重程度及其变化,分析疗效与基因型之间的关系。结果 HTR1A基因-1019C/G多态性,病例组G等位基因的频率(74.3%)明显高于对照组(65.6%)(P<0.05)。病例组HAMD总分各基因型组间总体比较差异有统计学意义(P<0.05),C/C基因型组高于C/G、G/G基因型组(P<0.05)。氟西汀治疗6周末,各基因型之间疗效比较差异无统计学意义,不同性别患者各基因型之间疗效比较差异无统计学意义。结论 HTR1A基因-1019C/G多态性与重性抑郁障碍之间存在关联,G等位基因可能是抑郁障碍的危险因子;C等位基因与重性抑郁障碍患者的病情严重程度存在关联,携带C/C基因型的患者病情可能较严重;该基因多态性与氟西汀的抗抑郁疗效可能无关。

Objective To explore whether major depressive disorder（MDD）and the therapeutic effect of fluoxetine are related to a functional polymorphism-1019C/G in the promoter region of the 5-HT1A receptor（HTR1A）gene.Methods Genotype and allele frequencies of HTR1A receptor gene-1019C/G polymorphism in MDD patients and healthy subjects（control）were examined by PCR-RFLP technique.Before and after the MDD patients accepted fluoxetine treatment for 6 weeks,17-item Hamilton depression rating scales（HAMD）were made to determine the severity of the symptoms,the outcome and remission status.Results There were significant differences in-1019C/G gene genotypes and alleles distribution between the patients and the healthy control,G allele frequency of the MDD patient was higher than that of the healthy control（P 0.05）.There were significant differences in HAMD scores among the patients with different genotypes in MDD group（P 0.05）,the score of C/C genotype patient was especially higher than that of C/G genotype（P 0.05）and G/G genotype patient（P =0.008）.There was no statistical difference in the therapeutic effect of fluoxetine among the patients with different genotypes in MDD group（P =0.761）.Conclusion HTR1A gene-1019C/G genetic polymorphism might related to MDD,especially G allele might be the possible risk factor of MDD.C allele might be correlated with the degree of pathogenetic severity,especially patients with the-1019C/C carriers.-1019C/G genetic polymorphism was not related to the clinical outcome of MDD patients treated with fluoxetine.