肿瘤坏死因子-α基因多态性与首发抑郁症及舍曲林疗效的关联研究

Research of tumor necrosis factor-αgene polymorphisms associated with first-episode depression and the efficacy of Sertraline

目的探讨肿瘤坏死因子-α(TNF-α)基因多态性与首发抑郁症及舍曲林疗效之间的相关性。方法选取2011年6月~2018年6月于滨州市优抚医院住院及门诊就诊的265例首发抑郁症患者作为病例组,另选取同期380名滨州市及周围市县的健康献血者作为对照组。采用聚合酶链反应-限制性片段长度多态性分析方法检测首发抑郁症患者、健康对照者各个多态性位点的基因型。采用SHEsis在线软件对TNF-α-G238A(rs361525)、-G308A(rs1800629)、-C857T(rs1799724)、-C863A(rs1800630)进行统计学分析。265例首发抑郁症患者使用舍曲林治疗8周后,以汉密尔顿抑郁量表(HAMD)评定疗效。结果病例组与对照组的rs1800629在基因型和等位基因频率分布比较,差异均有统计学意义(P<0.05),Bonferroni校正后,基因型频率分布比较差异仍有统计学意义(P<0.05)。而病例组与对照组的rs361525、rs1800630、rs1799724在基因型和等位基因频率分布比较,差异均无统计学意义(P>0.05)。病例组和对照组的单倍型频率分布比较,差异无统计学意义(P>0.05)。舍曲林治疗8周后,采用χ2检验分析首发抑郁症患者TNF-α基因4个SNPS多态性位点的等位基因和基因型频率分布与舍曲林疗效的关系,结果显示,有效组与无效组的rs1800629在基因型频率分布比较,差异无统计学意义(P>0.05),而等位基因频率分布比较,差异有统计学意义(P<0.05);Bonferroni校正后,等位基因频率分布比较,差异无统计学意义(P>0.05)。有效组与无效组的rs361525在基因型和等位基因频率分布比较,差异均有统计学意义(P<0.05);Bonferroni校正后,rs361525在基因型和等位基因频率分布比较,差异均有统计学意义(P<0.01)。有效组与无效组的rs1800630、rs1799724在基因型和等位基因频率分布比较,差异均无统计学意义(P>0.05)。有效组和无效组的单倍型频率分布比较,差异均无统计学意义(P>0.05)。结论TNF-α基因rs1800629多态性可能与首发抑郁症的易感性有关,rs361525多态性可能与舍曲林的疗效有关。

Objective To investigate the association between tumor necrosis factor-α(TNF-α)gene polymorphism with first-episode depression and efficacy of Sertraline.Methods A total of 265 inpatients and out-patients with first-episode depression diagnosed and treated in Binzhou Youfu Hospital from June 2011 to June 2018 were selected as the case group.In addition,380 healthy blood donors from Binzhou City and surrounding counties were selected as the control group.Each genotype polymorphism loci of patients with first-episode depression and healthy subjects was analyzed by the polymerase chain reaction-restriction fragment length polymorphism.SHEsis online software was used to analyze the differences in genotype distribution and allele distribution of TNF-α-G238A(rs361525)、-G308A(rs 1800629)、-C857T(rs1799724)、-C863A(rs1800630).Curative effect of 265 patients with first-episode depression treated with Sertraline after eight weeks was evaluated with Hamilton rating scale for depression(HAMD).Results Significant difference was shown in frequency distribution of genotypes and alleles of TNF-αgene rs1800629 between case group and control group(P<0.05);after Bonferroni correction,difference in frequency distribution of genotype was still significant(P<0.05).There was no significant difference in the frequency distribution of genotypes and alleles of rs361525 and rs1799724,rs1800630 between two groups(P>0.05).There was no significant difference in frequency of haploid type between case group and control group(P>0.05).After 8 weeks of Sertraline treatment,the chi-square test was used to analyze the relationship between the frequency distribution of alleles and genotypes of the 4 SNPS polymorphisms of TNF-αgene and the efficacy of Sertraline in patients with first-episode depression,the results showed that there was no significant difference in frequency distribution of genotype in rs1800629 between effective group and ineffective group(P>0.05);significant difference was shown in frequency distribution of allele in rs1800629 between two groups(P<0.05).After Bonferroni correction,no significant difference was shown in frequency distribution of allele in rs1800629 between effective group and ineffective group(P>0.05).Significant difference was shown in frequency distribution of genotypes and alleles of TNF-αgene rs361525 between effective group and ineffective group(P<0.05),after Bonferroni correction,difference in frequency distribution of genotypes and alleles in rs361525 was still significant(P<0.01).There was no statistically significant difference in genotype and allele frequency distribution of rs1800630 and rs1799724 between the effective group and the ineffective group(P>0.05).There was no significant difference in frequency of haploid type between effective group and ineffective group(P>0.05).Conclusion TNF-αgene rs1800629 polymorphism may be associated with the susceptibility of first-episode depression,rs361525 polymorphism may be associated with the efficacy of Sertraline.