FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea.
FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea.
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DOI：
10.3389/fnins.2023.1170889
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发表时间：
2023
影响因子：
4.3
通讯作者：
Li, Xinyi
中科院分区：
文献类型：
--
作者：
Wang, Anzhao;Wei, Zhicheng;Yuan, Haolin;Zhu, Yaxin;Peng, Yu;Gao, Zhenfei;Liu, Yuenan;Shen, Jinhong;Xu, Huajun;Guan, Jian;Yin, Shankai;Liu, Feng;Li, Xinyi
关键词：
阻塞性睡眠呼吸暂停（OSA）与精神疾病有关，特别是抑郁症和创伤后应激障碍（PTSD）。FKBP 5基因变异先前已被报道赋予抑郁症和PTSD的风险。本研究旨在探讨FKBP 5基因单核苷酸多态性（SNPs）与阻塞性睡眠呼吸暂停综合征（OSA）及其相关数量性状的关系。采用人体测量和多导睡眠图数据对5773名参与者进行FKBP 5基因内的4个SNP（rs 1360780、rs3800373、rs 9296158、rs 9470080）的基因分型。采用线性回归和Logistic回归分析FKBP 5单核苷酸多态性与OSA相关性状的关系。二元逻辑回归用于评估SNP对OSA易感性的影响。基于3DSNP数据库对SNPs的互作基因进行评估，并采用表达量性状基因座（eQTL）分析SNPs与基因表达的相关性。借助Brain Atlas进行人脑中的基因表达分析。在中度至重度OSA患者中，所有四种SNP均与AHIREM呈正相关，rs 9296158显示出最强的相关性（rs 9296158 = 1.724，p = 0.001）。进一步分层分析显示，在中度OSA男性中，rs 1360780、rs3800373和rs 9470080与觉醒时间呈正相关（分别为p = 0.0267、p = 0.0254和p = 0.0043）。rs 1360780和rs3800373更有可能被评定为更高级别的MAI类别（OR（95%CI）= 1.280（1.042 - 1.575），p = 0.019; OR（95%CI）= 1.294（1.052 - 1.592），p = 0.015）。rs 9296158和rs 9470080使睡眠效率低下的风险分别增加了25.7%和28.1%（OR（95%CI）= 1.257（1.003 - 1.575），p = 0.047; OR（95%CI）= 1.281（1.026-1.6），p = 0.029）。eQTL和基因表达模式的综合分析显示，4个SNPs可能通过调控FKBP 5、TULP 1和ARMC 12发挥作用。FKBP 5基因单核苷酸多态性与中重度OSA患者REM睡眠期间的睡眠呼吸事件相关，与中度OSA男性的睡眠结构变量相关。FKBP 5变异体可能是睡眠障碍的潜在易感因素，特别是在REM睡眠中。
Obstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). FKBP5 genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with OSA and OSA-related quantitative traits. Four SNPs within the FKBP5 gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between FKBP5 SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas. In moderate-to-severe OSA patients, all four SNPs were positively associated with AHIREM, and rs9296158 showed the strongest association (ß = 1.724, p = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time (p = 0.0267, p = 0.0254 and p = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 – 1.575), p = 0.019; OR (95% CI) = 1.294 (1.052 – 1.592), p = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 – 1.575), p = 0.047; OR (95% CI) = 1.281 (1.026–1.6), p = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating FKBP5, TULP1, and ARMC12. Single nucleotide polymorphisms in the FKBP5 gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.
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影响因子：
25.8
作者：
Fani, Negar;Gutman, David;Tone, Erin B.;Almli, Lynn;Mercer, Kristina B.;Davis, Jennifer;Glover, Ebony;Jovanovic, Tanja;Bradley, Bekh;Dinov, Ivo D.;Zamanyan, Alen;Toga, Arthur W.;Binder, Elisabeth B.;Ressler, Kerry J.
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影响因子：
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Dong, Hui;Chen, Ze-Ka;Huang, Zhi-Li
通讯作者：
Huang, Zhi-Li
影响因子：
7.4
作者：
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McLean, Samuel A.