The Val66Met polymorphism of the BDNF gene in anorexia nervosa: New data and a meta-analysis

The Val66Met polymorphism of the BDNF gene in anorexia nervosa: New data and a meta-analysis
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DOI:
10.3109/15622975.2011.605470
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发表时间:
2013-08-01
影响因子:
3.1
通讯作者:
Adan, Roger A. H.
Adan, Roger A. H.
中科院分区:
医学3区
文献类型:
--
作者:
Brandys, Marek K.;Kas, Martien J. H.;Adan, Roger A. H.

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目标. BDNF基因的Val 66 Met多态性(rs6265)是一种非同义多态性,以前与神经性厌食症(AN)有关。方法.我们对235例AN患者和643例对照进行了rs6265基因分型。此外,我们对所有在AN中检测该SNP的病例对照和基于家族的研究进行了系统回顾,并将结果合并到荟萃分析中。结果病例对照研究的结果无显著性。对于荟萃分析,确定并纳入了9项研究(n(病例)= 2,767; n(对照)= 3,322,n(trios)= 53)。首先,分析表明等位基因对比的OR为1.11(P = 0.024),Met等位基因的显性效应的OR为1.14(P = 0.025)。然而,额外的分析显示,第一个发表的研究(来自荟萃分析中的研究)过度影响了合并效应量(可能是由于一种称为赢家诅咒的现象)。当该病例对照研究被在很大程度上重叠的样本上进行的三重研究(n(trios)= 293)取代时,效应量变得更小且不显著,无论是等位基因对比(OR = 1.07,P = 0.156)还是显性效应(OR = 1.07,P = 0.319)。纳入研究的质量良好,各效应量之间无显著异质性。结论.我们的分析表明,BDNF Val 66 Met变异体在可检测水平上与AN无关。
Objectives. The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). Methods. We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis. Results. The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified (n(cases) = 2,767; n(controls) = 3,322, n(trios) = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 (P = 0.024) in the allelic contrast, and OR of 1.14 (P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study (n(trios) = 293) performed on a largely overlapping sample, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes. Conclusions. Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels.