The tryptophan hydroxylase gene influences risk for bipolar disorder but not major depressive disorder: results of meta-analyses
The tryptophan hydroxylase gene influences risk for bipolar disorder but not major depressive disorder: results of meta-analyses
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DOI：
10.1111/j.1399-5618.2008.00623.x
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发表时间：
2008-11-01
影响因子：
5.4
通讯作者：
Tsuang, Ming T.
中科院分区：
文献类型：
--
作者：
Chen, Christine;Glatt, Stephen J.;Tsuang, Ming T.
目的：色氨酸羟化酶是5-羟色胺合成的限速酶，因此其基因TPH作为双相情感障碍和重度抑郁症的危险因素已被广泛研究。本报告的目的是综合关于这些假定关联的现有数据，并得出TPH对情绪障碍风险影响的性质和程度的最佳估计。方法：我们使用PubMed在线搜索引擎确定了研究TPH A218 C多态性与重度抑郁症或双相情感障碍相关的研究，结果：AA基因型与CC或AC基因型相比对双相情感障碍的风险有显著影响，提示A等位基因可能以隐性方式增加双相情感障碍的风险。没有三种基因型显着增加的风险为重性抑郁症相对于任何其他genotype.Conclusion：纯合隐性基因型的TPH A218 C多态性有一个显着的双相情感障碍的风险，但不重性抑郁症的影响。对这些结果的一个可能的解释是，A等位基因通过允许或促进躁狂而对抑郁没有影响，从而影响情绪。进一步复制这些。在将TPH确定为双相情感障碍的危险基因之前，还需要更多的病例对照和基于家族的关联研究结果。
Objective: Tryptophan hydroxylase is the rate-limiting enzyme in the synthesis of serotonin, and thus its gene, TPH, has been extensively studied as a risk factor for both bipolar disorder and major depressive disorder. The purpose of the present report is to synthesize the available data on these putative associations and derive best estimates of the nature and magnitude of the influence of TPH on risk for mood disorders.Methods: We identified studies that examined the TPH A218C polymorphism in relation to major depressive disorder or bipolar disorder using the PubMed online search engine, ultimately including 10 case-control studies in two meta-analyses.Results: The AA genotype had a significant effect on risk for bipolar disorder in comparison to either the CC or AC genotypes, suggesting that the A allele may increase risk for bipolar disorder in a recessive manner. None of the three genotypes significantly increased risk for major depressive disorder relative to any of the other genotypes.Conclusion: The homozygous recessive genotype of the TPH A218C polymorphism has a significant effect on risk for bipolar disorder but not major depressive disorder. A possible explanation for these results is that the A allele influences mood by permitting or facilitating mania while having no effect on depression. Further replication of these. findings in additional large case-control and family-based association is needed before TPH can be designated a risk gene for bipolar disorder.