血浆同型半胱氨酸水平及N^5,N^(10)-亚甲四氢叶酸还原酶基因多态性与老年期抑郁症的关联研究

The association of plasma homocysteine level, methylene tetrahydrofolate reductase gene polymorphism and depression in the elderly

目的探讨血浆同型半胱氨酸(Hcy)水平及N5,N10-亚甲四氢叶酸还原酶(MTHFR)基因多态性与老年期抑郁症发病的关系。方法采用毛细管电泳-紫外检测法、聚合酶链反应-限制性片段长度多态性技术测定60例老年期抑郁症患者(抑郁症组)和80名正常人(对照组)的血浆总Hcy水平和MTHFR基因多态性。患者入组时评定汉密尔顿抑郁量表(HAMD),治疗第6周末评定疗效(HAMD减分率≥50%为有效,<50%为无效)。结果(1)抑郁症组的血浆Hcy水平[(17±6)μmol/L]明显高于对照组[(12±4)μmol/L],差异有统计学意义(P<0.01)。<60岁首次发病(以下简称首发)患者(n=30)的血浆Hcy水平[(16±5)μmol/L]与≥60岁首发患者[n=30,(19±6)μmol/L]的差异无统计学意义(P>0.05);单次发作患者(n=17)的血浆Hcy水平[(18±6)μmol/L]与反复发作患者[n=43,(17±5)μmol/L]的差异无统计学意义(P>0.05);伴心脑血管疾病患者(n=27)的血浆Hcy水平[(19±6)μmol/L]与不伴心脑血管疾病患者[n=33,(16±5)μmol/L]的差异无统计学意义(P>0.05);治疗有效患者(n=40)的血浆Hcy水平[(18±5)μmol/L]与治疗无效患者[n=20,(17±6)μmol/L]的差异无统计学意义(P>0.05)。(2)抑郁症组治疗前后HAMD评分的减分率与血浆Hcy水平无显著相关性(P>0.05)。(3)MTHFRC677T基因型有3种,即纯合子突变型(T/T)、杂合子突变型(T/C)和野生型(C/C)。抑郁症组的基因型及等位基因频率与对照组比较,差异均无统计学意义(P>0.05)。抑郁症组患者的首发年龄、发病次数、是否伴发心脑血管疾病及抗抑郁药治疗第6周末的疗效与MTHFRC677T基因型分布均无关联(P>0.05)。(4)不同基因型的受试者(不论是抑郁症组还是对照组)血浆Hcy水平的差异无统计学意义(P>0.05)。结论血浆Hcy水平升高可能是老年期抑郁症发病的一个独立危险因素。

Objective To investigate the relationship between plasma homocysteine （Hcy） and methylenetetrahydrofolate reductase （MTHFR） gene polymorphism and gerontic depression. Methods Sixty elderly with major depression and 80 healthy controls were involved in the study. The plasma Hcy level was determined with the capillary electrophoresis ultraviolet detection, and the MTHFR gene polymorphisms with the polymerase chain reaction-restriction fragment length polymorphism assay. The patients were assessed with the Hamilton Rating Scale for Depression （HAMD） before and after 6-week treatment. Results The plasma Hcy level in the patients [ （ 17 ±6） μmol/L] was significantly higher than that in the controls[ （ 12 ± 4）μmol/L] （ P 〈 0. 01 ）. The reduction rate of HAMD score was not significantly correlated to the plasma Hcy level in patients （ r = - 0. 137, P = 0. 445 ）. There were no significant differences on thegenotypes and alleles distribution of the MTHFR gene C677T polymorphisms between patients and controls（ P 〉 0. 05 ）. Conclusion The elevated plasma Hcy level may be a risk factor for major depression in the elderly.