5-羟色胺转运蛋白基因多态性与抑郁症临床表型的关联性

The 5-HTT gene polymorphisms correlated with the clinical manifestations of depression

目的探讨5-羟色胺转运蛋白基因5-HTFLPR及STin2与抑郁症临床症状的关联性。方法研究共纳入401名中国汉族抑郁症患者，提取外周血基因组DNA，采用PCR分别对5-HTTLPR及STin2进行基因多态性分析；同时对每位患者进行HAMD-17及HAMA量表评估；然后进行关联性分析。结果（1）5-HTfLPR各基因型患者发病年龄分布差异有统计学意义（F=3．281，P=0．039），L／S组患者发病年龄最小，I／L组患者发病年龄最大。同时三组基因型患者的HAMA1条目（焦虑心境）得分差异具有统计学意义（P=0．010），其中L／S组患者得分[（2．34±0．80）分]显著高于S／S组患者[（2．08±0．85）分，校正P=0．018]。（2）STin2各基因型患者的HAMD10（精神性焦虑）、HAMA1（焦虑心境）、HAMA3（害怕）条目及精神性焦虑因子评分差异均具有统计学意义（P值分别为：O．014、0．044、0．036及0．006），其中12／10基因型组患者得分最高[分别为：（2．40±0．83）分、（2．38±0．90）分、（1．42±1．04）分、（14．60±4．26）分）]，与12／12组患者相比，HAMD10（精神性焦虑）条目[（2．11±0．77）分]及精神性焦虑因子得分[（12．96±3．78）分]均差异具有统计学意义（校正JP值分别为：0．018、0．006）。结论在中国汉族抑郁症人群中，5-HTTLPR与抑郁症发病年龄相关；5-HTFLPR及STin2两种基因多态性均与患者焦虑样症状表型存在关联，杂合子患者的焦虑症状更为突出，为抑郁症临床分型及优化治疗提供了一定线索。

Objective To determine the potential correlation of 5-HTT gene polymorphisms （ 5-HT- TLPR and STin2） with clinical manifestations in depression. Methods A total of 401 depressed patients, all of Chinese Han region ,were collected and genotyped by polymerase chain reactions （PCR）. All patients were evaluated using a 17-item Hamilton depression rating scale （HAMD-17） and Hamihon anxiety rating scale （HAMA） , and then associated analysis was applied. Results （ 1 ） The age of onset in patients with L/S genotype of 5-HTLPR polymorphism were much younger than that of patients with L/L and S/S genotype （F= 3.281, P= 0.039）. Besides, there was also a significant difference of HAMA1 （anxious mood） scores among patients with different genotypes for 5-HTFLPR polymorphism,where the scores of those with L/S genotype were the highest （2.34±0.80, P= 0.010）. （2） The scores of HAMD10 （mental anxiety）, HAMA1 （anxious mood）, HAMA3 （fear） and mental anxiety factor were higher in patients with 12/10 genotype than patients with 12/12 and 10/10 genotype for STin2 polymorphism （2.40±0.83,2.38±0.90,1.42±1.04,14.60±4.26 respectively; P value ：0.014,0.044,0.03 and 0.006 respectively）.The scores of HAMD10（ mental anxiety） and mental anxiety factor were （2.11±0.77）, （12.96±3.78） in the 12/12 genotype patients, and significantly lower than that in the 12/10 genotype patients （adjusted P value： 0.018,0.006）.Conclusions A positive association of the 5-HTT polymorphisms with anxious symptoms in depressed patients is revealed. These findings might provide some evidences for the clinical phenotype and optimization of depression treatment.