González-Castro Thelma Beatriz, Nicolini Humberto, Lanzagorta Nuria, López-Narváez Lilia, Genis Alma, Pool García Sherezada, Tovilla-Zárate Carlos Alfonso
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco.
Bipolar Disord. 2015 Feb;17(1):27-38. doi: 10.1111/bdi.12227. Epub 2014 Jul 8.
The aim of this study was to evaluate the association of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta-analysis and (ii) a case-control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features.
We performed a keyword search of the PubMed and Web of Science databases. A total of 22 studies that have investigated the association of Val66Met (rs6265) with bipolar disorder were selected for inclusion and combined with random effects meta-analysis, using allelic, additive, dominant, and recessive models. Finally, the single nucleotide polymorphism (rs6265) Val66Met in the BDNF gene was genotyped and compared between 139 patients with bipolar disorder and 141 healthy volunteers in a Mexican population.
The pooled results from the meta-analysis (9,349 cases and 7,437 controls) did not show a significant association in any of the models. The same results were obtained in our case-control study when analyzing the distribution of the genotypic frequencies of the Val66Met polymorphism in patients with bipolar disorder. However, when we analyzed the association between rs6265 and lifetime history of suicidal behavior, we found an association between genotype Val-Val and suicide attempt (p = 0.02).
Although the present study has some limitations, the results indicate a lack of association between the Val66Met polymorphism and bipolar disorder. However, in our case-control study in a Mexican population, the Val66Met polymorphism was associated with suicidal behavior in patients with bipolar disorder. Nevertheless, it is important to consider potential interactions of the BDNF gene, the environment, and different inheritance patterns, when carrying out future genetic studies with larger samples.
本研究旨在通过（i）一项荟萃分析和（ii）一项针对墨西哥人群的病例对照研究，评估脑源性神经营养因子（BDNF）基因Val66Met多态性与双相情感障碍的关联。我们还研究了这种多态性与临床特征之间的可能关联。
我们对PubMed和Web of Science数据库进行了关键词搜索。共筛选出22项研究，这些研究调查了Val66Met（rs6265）与双相情感障碍的关联，并纳入研究，采用等位基因、加性、显性和隐性模型进行随机效应荟萃分析。最后，对墨西哥人群中139例双相情感障碍患者和141名健康志愿者的BDNF基因单核苷酸多态性（rs6265）Val66Met进行基因分型并比较。
荟萃分析（9349例病例和7437例对照）的汇总结果在任何模型中均未显示出显著关联。在我们的病例对照研究中，分析双相情感障碍患者中Val66Met多态性的基因型频率分布时也得到了相同的结果。然而，当我们分析rs6265与自杀行为终生史之间的关联时，发现Val-Val基因型与自杀未遂之间存在关联（p = 0.02）。
尽管本研究存在一些局限性，但结果表明Val66Met多态性与双相情感障碍之间缺乏关联。然而，在我们针对墨西哥人群的病例对照研究中，Val66Met多态性与双相情感障碍患者的自杀行为有关。尽管如此，在未来进行更大样本量的基因研究时，考虑BDNF基因、环境和不同遗传模式之间的潜在相互作用非常重要。
