重性抑郁障碍患者5-羟色胺转运体基因启动子区多态性研究

Association of serotonin transporter gene promoter region polymorphisms with major depressive disorder

目的探讨5-羟色胺转运体基因启动子区多态性与重性抑郁障碍发病的关联。方法采用病例对照研究方法，选取350例重性抑郁障碍患者和370例与之性别、年龄相匹配的健康对照作为研究对象，采用汉密尔顿抑郁量表（HAMD-17）评定抑郁症状的严重程度，抽取被试外周静脉全血，提取基因组DNA，采用限制性片段长度多态性-聚合酶链反应方法（PCR—RELP）对5-羟色胺转运体基因启动子区（5-HTYLPR／rs25531）多态性进行分型。运用SPSS19．0进行数据分析。结果病例组5-HTFLPR基因分布（LL、Ls、ss基因型频率分别为10．9％，38．0％，51．1％，L、S等位基因频率分别为29．9％、70．1％）与对照组（LL、LS、SS基因型频率分别为12．4％，40．5％，47．1％，L、S等位基因频率分别为32．7％、67．3％）相比差异均无统计学意义（P=0．522；P=0．245）；而病例组5-HTTLPR／rs25531基因分布（L’L’、L’S’、S’S’基因型频率分别为6．6％，34．5％，58．9％，L’、S’等位基因频率分别为21．7％、78．3％）与对照组（L’L’、L’s’、s’s’基因型频率分别为8．1％，42．4％，49．5％，L’、S’等位基因频率分别为29．3％，70．7％）相比差异均有统计学意义（P=0．041；P=0．019）。单因素Logistic回归分析，与L’L’（LALA）相比，S’S’（SS，LGS，LG：LG）为重性抑郁障碍发病的危险基因型（P：0．016，OR=1．461，OR95％CI=1．072～1．991）。结论尚不能认为5-HTrLPRL／S基因多态性与重性抑郁障碍发病有关联，5-HTYLPR／rs25531S’S’基因型与s’（S，LG）等位基因可能为重性抑郁障碍发病的危险因子。

Objective To explore the association of serotonin transporter gene promoter region polymor- phisms with the onset of major depressive disorder. Methods A case-control association study was taken ,350 pa- tients which met the diagnostic and statistical manual of mental disorders in the fourth edition （DSM-IV） criteria for major depressive disorder （MDD）, and 370 age- and gender-matched controls were recruited. HAMD-17 was used to evaluate the severity of depression. Peripheral blood of all the objects was collected, and genomic DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLP） was used to detect 5-HTTLPR/rs25531 genotypes. SPSS19.0 statistical software was used for statistical analysis. Results The 5-HT- TLPR genotypes and alleles frequency distribution between MDD patients （LL, LS, SS genotypes： 10. 9%, 38.0% ,51.1% ; L, S alleles ： 29.9% ,70.1% ） and controls （ LL, LS, SS genotypes ： 12.4% ,40.5 % ,47.1% ; L, S alleles ： 32.7 % ,67.3 % ） had no significant difference （ P = 0. 522 ; P = 0. 245 ）. However, the frequency of 5-HITLPR/rs25531 genotypes and alleles distribution between MDD patients （L＇ L＇, L＇ S＇ , S＇ S＇ genotypes： 6.6% ,34.5%,58.9%; L＇,S＇ alleles： 21.7%,78.3%）and controls（L＇L＇,L＇S＇,S＇S＇ genotypes：8.1%, 42.4% ,49.5% ;L＇ ,S＇ alleles ：29.3% ,70. 7% ） had statistically significance （ P = 0. 041 ; P = 0. 019）. Logistic regression a- nalysis showed that S＇S＇ （SS,LGS,LGLG ） was the risk genotype for MDD （P =0. 016, OR = 1. 461, OR 95% C1 = 1. ff72- 1.991 ）. Conclusion No significant association was found between 5-HTI]_PR polymorphism and the onset of major depres- sive disorder,5-HTILPR/rs25531 S＇ S＇ genotype and S＇ maybe the risk genes.