School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Sci Rep. 2016 Sep 7;6:32687. doi: 10.1038/srep32687.
Previous studies have investigated the association between common variants in FKBP5 and MDD; however, the results remain inconsistent. In order to conduct a comprehensive meta-analysis of the association between FKBP5 variants and MDD risk, seven studies involving 26582 subjects, including 12491 cases with MDD and 14091 controls, were enrolled totally. Four common SNPs (rs1360780, rs4713916, rs3800373 and rs755658) with complete data from two or more studies were analyzed. In the total sample, there was no evidence of a significant association between MDD and any of the four SNPs using a random-effects model. However, after removing one heterogeneous German study, as indicated by sensitivity analysis, both the rs1360780 T-allele (Z = 2.95, P = 0.003, OR = 1.06, 95% CI = 1.02-1.11) and the rs3800373 C-allele (Z = 3.05, P = 0.002, OR = 1.07, 95% CI 1.02-1.12) were significantly associated with MDD in a fixed-effect model. Our study thus provides support for an association between specific FKBP5 genetic variants and MDD risk. Rs4713916 was not significantly associated with MDD; However, this analysis had limited statistical power and larger sample sizes are required to further validate this result. Future research should also investigate possible gender- and ethnicity-specific differences in the association between FKBP5 and MDD.
先前的研究已经调查了 FKBP5 常见变体与 MDD 之间的关联;然而,结果仍然不一致。为了对 FKBP5 变体与 MDD 风险之间的关联进行全面的荟萃分析,共纳入了 7 项研究,涉及 26582 名受试者,包括 12491 例 MDD 患者和 14091 例对照。对来自两项或更多研究的具有完整数据的四个常见 SNP(rs1360780、rs4713916、rs3800373 和 rs755658)进行了分析。在总样本中,使用随机效应模型没有发现 MDD 与任何四个 SNP 之间存在显著关联。然而,经过敏感性分析,去除一个具有异质性的德国研究后,rs1360780 T 等位基因(rs1360780 T-allele)(Z=2.95,P=0.003,OR=1.06,95%CI=1.02-1.11)和 rs3800373 C 等位基因(rs3800373 C-allele)(Z=3.05,P=0.002,OR=1.07,95%CI 1.02-1.12)在固定效应模型中与 MDD 显著相关。因此,我们的研究为特定 FKBP5 遗传变异与 MDD 风险之间的关联提供了支持。rs4713916 与 MDD 无显著关联;然而,这项分析的统计效力有限,需要更大的样本量来进一步验证这一结果。未来的研究还应调查 FKBP5 与 MDD 之间关联的可能存在的性别和种族特异性差异。