缺血性脑卒中后抑郁与TPH2 rs4641528位点多态性的关联及危险因素分析

Association of post-stroke depression with tryptophan hydroxylase 2 rs4641528 polymorphism and risk factors of post-stroke depression

目的探讨缺血性脑卒中后抑郁(PSD)与色氨酸羟化酶2(TPH2)基因多态性及相关临床危险因素之间的关联。方法选择自2015年3月至2017年9月收治于皖南医学院弋矶山医院神经内科卒中病房并首次被诊断为急性脑梗死的患者376例,根据Hamilton抑郁量表及精神疾病诊断与统计手册第4版(DSM-Ⅳ)诊断标准诊断PSD,并将患者分为PSD组(n=104)和非PSD组(n=272)。采用高分辨熔解曲线分析法对入组患者进行TPH2基因rs464152、rs1386494位点基因分型,分析不同基因型及等位基因与PSD的相关性;并对单因素分析中差异有统计学意义的项目行多因素Logistic回归分析,明确影响PSD的独立危险因素。结果PSD组患者104例,非PSD组患者272例。2组患者受教育年限、基线卒中功能缺损程度[美国国立卫生研究院卒中量表(NIHSS)评分]差异有统计学意义(P<0.05)。2组患者间rs1386494基因型和等位基因频率差异均无统计学意义(P>0.05);rs4641528基因型和等位基因频率差异均有统计学意义(P<0.05)。PSD组患者C等位基因占54.3%,非PSD组患者C等位基因占43.4%,等位基因C的存在增加了PSD发病风险(P=0.007,OR=1.552,95% CI:1.126~2.141)。多因素Logistic回归分析结果显示,基线NIHSS评分、rs4641528位点(CC+CT)基因型是PSD的独立影响因素。结论皖南地区人群中,TPH2 rs4641528位点基因多态性、基线NIHSS评分与缺血性脑卒中后3个月时PSD存在关联。

Objective To investigate the association of post-stroke depression (PSD) with tryptophan hydroxylase 2 (TPH2) gene polymorphism and related clinical risk factors of PSD. Methods Three hundred and seventy-six patients diagnosed as having acute ischemic stroke for the first time, admitted to our hospital from March 2015 to September 2017, were chosen in our study. According to Hamilton depression scale scores and Diagnostic and statisistical Manual of Mental Disorders, fourth edition (DSM-IV), these patients were divided into PSD group and non-PSD group. High-resolution melt analysis was used to complete the genotyping of TPH2 gene rs4641528 and rs1386494 in the enrolled patients. The correlations of single nucleotide polymorphisms and PSD were analyzed. Logistic regression analysis was performed on items with statistically significant differences in univariate analysis to identify independent factors affecting PSD. Results There were 104 patients into the PSD group and 272 patients into the non-PSD group;there were statistically significant differences between the two groups in years of education and NIHSS scores (P<0.05). There were no significant differences in rs1386494 genotype and allele frequency between the two groups (P>0.05);there were significant differences in rs4641528 genotype and allele frequency between the two groups (P> 0.05). The C allele in the chromosomes of PSD patients accounted for 54.3%, while the C allele in the chromosomes of non-PSD patients accounted for 43.4%;the presence of allele (C) increased the risk of PSD (OR=1.552, 95%CI: 1.126-2.141, P=0.007). The results of multivariate Logistic regression analysis showed that baseline NIHSS scores and genotypes of rs4641528 (C/C+C/T) were independent influencing factors of PSD. Conclusion TPH2 rs4641528 gene polymorphism and baseline NIHSS scores are found to be associated with depression 3 months after stroke in south Anhui province.