【摘要】 目的 探讨中国汉族TPH A218C多态性与抑郁症及症状表型的相关性。方法 采用PCRRFLP方法研究70例抑郁症(重性抑郁症)患者的TPH基因的多态性分布；采用汉密尔顿抑郁量表(HAMD)评定症状表型。结果 抑郁症组TPH A218C多态性的等位基因C的频率(44.3%)明显高于对照组(24.3%)，而A等位基因的频率(55.7%)和A/A基因型的频率(31.4%)显著低于对照组(75.7%和62.9%)(χ2=6.214 ，P=0.013)；(χ2=6.946, P=0.031)。按性别分层后，男性抑郁症组C/C基因型的频率(12.5%)明显高于对照组(6.3%)，而A/A基因型的频率(25.0%)显著低于对照组(75.0%)(χ2=8.103, P=0.017)；病例组中症状表型在三种基因型间分布无显著性差异。结论 TPH A218C基因的多态性与抑郁症发病相关，其相关性受性别影响，而与症状表型间无明显的关联。
【关键词】 抑郁症；色氨酸羟化酶基因；多态性
Association of TPH gene polymorphism with major depression and symptom phenotypes
ABSTRACT: Objective To explore the association among the depression, symptom phnotypes and polymorphism TPH A218C in the Han Chinese. Methods TPH A218C was determined using a PCRbased technique. TPH was genotyped using restriction fragment length polymorphism in 70 patients affected by depression and 70 unrelated controls.We evaluated the symptom phenotypes of cases applying the Hamilton Rating Scale for depression(HAMD). Results The TPH A218C genotype distribution in 70 patients with major depression was significantly different from that in controls (χ2=6.946, P=0.031). The C allele in patients (44.3%) was significantly more frequent than in controls (24.3%) but the A allele (55.7%) and A/A genotype (31.4%) were significantly less frequent than in controls (75.7% and 62.9%) (χ2=6.946, P=0.031). Meanwhile, among the males, a trend was observed toward an excess of TPH C/C (12.5% vs. 6.3%) in patients and excess of TPH A/A in controls (75.0% vs. 25.0%) (χ2=8.103, P=0.017). There were no significant differences in three genotypes distribution among symptom phenotypes of cases. Conclusion There was an association between TPH A218C polymorphism and depression. The findings raise the possibility that TPH A218C polymorphism may exert differential effects based on gender. There is no association among TPH A218C polymorphism and symptom phenotypes of depression.
KEY WORDS: depression; tryptophan hydroxylase gene; polymorphism
色胺酸羟化酶(tryptophan hydroxylase, TPH)是5羟色胺(5hydroxytryptamine, 5HT)合成的限速酶，它将色氨酸羟化为5羟色酚后经脱羧作用转化成5HT，决定活体5HT的水平。TPH的改变是5HT水平改变的可能原因之一，而5HT神经递质的改变与一些精神障碍和行为异常(包括抑郁、自杀)有关[16]。TPH基因定位于11号染色体短臂14-15.3区(11p14-p15.3)，约长29kb，至少包括11个外显子，一个5’端非转录区。在内含子7中存在两种多态性，即在779和218位核苷酸处出现A/C置换，而且这两种多态性呈不平衡紧密连锁。TPH A218C多态性与抑郁症的关系在国外虽然有了一些研究，但结论尚不一致。国内仅有一篇此方面的报道。
1 对象与方法
1.1 研究对象 病例组：选自2005年1月-2005年12月西安交通大学医学院第一附属医院精神卫生中心的门诊及住院患者。纳入和排除标准：①年龄≥16岁；②中国汉族；③汉密尔顿抑郁量表(Hamiltons Depression Scale, HAMD)17项评分测评总分≥18；④符合美国精神障碍诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental DisordersFour, DSMIV)[7]重性抑郁障碍(单次发作或反复发作)的诊断标准；⑤病程＜3年；⑥入组前两周未用任何抗抑郁及抗精神病药物治疗；⑦无严重躯体疾病或脑器质性疾病；⑧排除伴发于其他精神障碍的抑郁状态；⑨排除物质滥用或依赖者,排除有双相情感障碍家族史者；⑩本人知情同意。
对照组：纳入和排除标准：①年龄≥16岁；②中国汉族；③汉密尔顿抑郁量表(HAMD)17项评分测评总分＜5分；④无严重躯体疾病或脑器质性疾病；⑤无精神疾病及病史；⑥无物质滥用或依赖者；⑦家族
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