Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis
Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis
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DOI：
10.1038/sj.mp.4001663
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发表时间：
2005-08-01
影响因子：
11
通讯作者：
Collier, DA
中科院分区：
文献类型：
--
作者：
Cho, HJ;Meira-Lima, I;Collier, DA
5-羟色胺转运体（5-HTT）是双相情感障碍（BPD）的候选基因。在一系列研究中，它与疾病的关系已经被调查过，但总体结果不一致，它在疾病中的作用仍然存在争议。使用荟萃分析技术的系统评价是客观和可重复地评估单个研究并产生综合结果的有用方法。我们对已发表的研究进行了两项荟萃分析-基于人群和基于家族的研究-调查BPD与5-HTT基因连锁多态性区域（5-HTTLPR）和内含子2可变数目串联重复序列（VNTR）多态性之间的关联。使用Medline和Embase检索文献，以确定纳入的研究。我们在统计学上将基于人群和基于家庭的研究合并为一项荟萃分析。对于这两种多态性，我们的综述显示了显著的合并优势比（OR）：5-HTTLPR为1.12（95%CI 1.03 - 1.21），内含子2 VNTR为1.12（95%CI 1.02 - 1.22）。荟萃回归分析显示，研究类型（基于人群vs基于家族; 5-HTTLPR P = 0.41，内含子2 VNTR P = 0.91）和样本种族（白人vs非白人; 5-HTTLPR P = 0.35，内含子2 VNTR P = 0.66）均未显著影响荟萃分析的异质性。观察到的OR可以简单地认为是5-HTT的一个非常小但可检测的效应，当与其他易感性基因座结合时具有累加效应。关于这一发现的替代假设也进行了讨论：涉及两个多态性或其他SNP标记的单倍型的更强的影响;这些多态性对BPD的特定表型的更直接的影响;以及基因-环境相互作用作为5-HTT遗传效应的介导者的存在。
The serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using meta-analytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies - both population-based and family-based studies - investigating the association between BPD and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats ( VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03 - 1.21) for the 5-HTTLPR and 1.12 ( 95% CI 1.02 - 1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type ( population-based vs family-based; P = 0.41 for the 5-HTTLPR and P = 0.91 for the intron 2 VNTR) nor the sample ethnicity ( Caucasian vs non-Caucasian; P = 0.35 for the 5-HTTLPR and P = 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene - environment interaction as a mediator of the genetic effects of 5-HTT.