Li Dawei, He Lin
Bio-X Center, Shanghai Jiao Tong University, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, People's Republic of China.
Hum Genet. 2006 Aug;120(1):22-30. doi: 10.1007/s00439-006-0190-5. Epub 2006 Jun 2.
A number of studies have suggested an association between schizophrenia and the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent in schizophrenia. In an attempt to clarify this inconsistency our meta-analysis has combined all the studies using multiple research methods published up to February 2006 to give a comprehensive picture of the role of three hydroxylase-related genes. The TPH A218C/A779C (OR = 1.18, 95% C.I. 1.06-1.33, P = 0.004) revealed a significant association with schizophrenia. However, the evidence for the TH and phenylalanine hydroxylase (PAH) genes was weak. No publication bias was detected in current studies. The findings, which may implicate the involvement of TPH in the pathogenesis of schizophrenia, have potentially important clinical, scientific and public health implications as well as providing a putative basis for the study of hydroxylase-related drugs. To our knowledge, this is the first meta-analysis of association between the three genes and schizophrenia.
多项研究表明,精神分裂症与色氨酸羟化酶(TPH)和酪氨酸羟化酶(TH)基因之间存在关联。另一方面,一些试图重复这些发现的研究结果却参差不齐,这可能反映出个别研究的统计效力不足以及精神分裂症本身固有的异质性。为了澄清这种不一致性,我们进行了一项荟萃分析,综合了截至2006年2月发表的所有使用多种研究方法的研究,以全面了解三种羟化酶相关基因的作用。TPH A218C/A779C(比值比=1.18,95%可信区间1.06 - 1.33,P = 0.004)显示与精神分裂症存在显著关联。然而,TH基因和苯丙氨酸羟化酶(PAH)基因的证据较弱。在当前研究中未检测到发表偏倚。这些发现可能暗示TPH参与了精神分裂症的发病机制,具有潜在重要的临床、科学和公共卫生意义,也为羟化酶相关药物的研究提供了一个假定基础。据我们所知,这是首次对这三种基因与精神分裂症之间的关联进行荟萃分析。