Biological psychiatry Laboratory, Tianjin Mental Health Institute, Tianjin Anding Hospital, Tianjin, China.
University of Groningen, University Medical Centre Groningen, University Centre of Psychiatry, Groningen, the Netherlands.
Medicine (Baltimore). 2021 Sep 10;100(36):e26983. doi: 10.1097/MD.0000000000026983.
The identification of single-nucleotide polymorphisms (SNPs) in genes putatively related to pathophysiological processes in major depressive disorder (MDD) might improve both diagnosis and personalized treatment strategies eventually leading to more effective interventions. Considering the important role of the glucocorticoid receptor and the related FK506 binding protein 51 (FKBP51) in the pathophysiology of MDD, we aimed to investigate putative associations between variants of FKBP5, the coding gene of FKBP51, with antidepressant treatment resistance and MDD susceptibility.Nine common SNPs of the FKBP5 gene prioritized based on location and, putative or known functions were genotyped in Han Chinese population, including MDD patients with or without antidepressant-treatment resistance and healthy controls. Associations of FKBP5 SNPs with MDD susceptibility and treatment response were examined in the whole group of MDD patients, as well as in subgroups stratified by antidepressant treatment resistance, compared with healthy controls.In total, 181 Han Chinese patients with MDD and 80 healthy controls were recruited. No significant SNP or haplotype associations were observed in the whole patient group. There were nominal significant differences both for the haplotype block with SNPs in strong LD (r2 > 0.8, P = .040) and haplotype block with SNPs in moderate LD (r2 > 0.1, P = .017) between the haplotype distributions of patients with antidepressant treatment resistance (n = 81) and healthy controls, but both significances did not survive multiple testing correction. Furthermore, no specific haplotype could be observed causing a significant difference in any combination between all comparisons.No associations were observed of FKBP5 variants with MDD or antidepressant treatment response. The lack of associations might be due to the relatively small sample size of this study (power ranged from 0.100 to 0.752). A follow-up study will need larger, better phenotyped, and more homogeneous samples to draw a definitive conclusion regarding the involvement of this gene in MDD.
单核苷酸多态性（SNP）在基因中的鉴定，这些基因推测与重度抑郁症（MDD）的病理生理过程有关，可能会提高诊断和个性化治疗策略的效果，最终导致更有效的干预措施。考虑到糖皮质激素受体及其相关 FK506 结合蛋白 51（FKBP51）在 MDD 病理生理学中的重要作用，我们旨在研究 FKBP51 的编码基因 FKBP5 中的变体与抗抑郁治疗抵抗和 MDD 易感性之间的潜在关联。根据位置和潜在或已知功能，对 FKBP5 基因的 9 个常见 SNP 进行了优先排序，并对汉族人群进行了基因分型，包括有或无抗抑郁治疗抵抗的 MDD 患者和健康对照者。在整个 MDD 患者组以及根据抗抑郁治疗抵抗分层的亚组中，检查了 FKBP5 SNP 与 MDD 易感性和治疗反应的关联，与健康对照组进行了比较。共招募了 181 名汉族 MDD 患者和 80 名健康对照者。在整个患者组中，没有观察到 SNP 或单体型的显著关联。在具有强 LD（r2>0.8，P=0.040）的 SNP 单体型块和具有中度 LD（r2>0.1，P=0.017）的 SNP 单体型块之间，具有抗抑郁治疗抵抗（n=81）的患者和健康对照组之间的单体型分布均存在显著差异，但均未通过多重检验校正。此外，在任何比较组合中，都没有观察到特定的单体型导致显著差异。没有观察到 FKBP5 变体与 MDD 或抗抑郁治疗反应之间存在关联。这种缺乏关联可能是由于本研究的样本量相对较小（功效范围从 0.100 到 0.752）。后续研究需要更大、更好表型和更同质的样本，以对该基因在 MDD 中的参与得出明确的结论。
