Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients

Lou, Qiu yue; Li, Zhen; Teng, Ying; Xie, Qiao Mei; Zhang, Man; Huang, Shun; Li, Wen Fei; Chen, Yang Fan; Pan, Fa Ming; Xu, Shaohua; Cai, Jing; Liu, Shuang; Jin, Tao; Liu, Sheng Xiu; Huang, Hai; Wang, Fang; Pan, Hai; Su, Hong; Xu, Zhiwei; Zou, Yan

doi:10.1007/s10067-020-05195-0

Cited by 23 publications

(20 citation statements)

References 44 publications

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“…Compared with controls, FKBP4 mRNA expression was decreased in the endometrium of women with endometriosis . The rs12582595 of FKBP4 was correlated with general health improvement in systemic lupus erythematosus patients (Lou et al, 2020). The FKBP4 SNP rs4409904 was associated with lower odds of polycystic ovary syndrome.…”

Section: Discussionmentioning

confidence: 94%

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

Jia

Xie

et al. 2021

Front. Genet.

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BackgroundLung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.MethodsWe obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.ResultsWe found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD.ConclusionsThe expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.

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Section: Discussionmentioning

confidence: 94%

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

Jia

Xie

et al. 2021

Front. Genet.

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“…Glucocorticoid receptor polymorphisms were reported to be associated with increased sensitivity to glucocorticoids, leading to a higher prevalence of features associated with hypercortisolism and efficacy of glucocorticoids or, by contrast, a relative glucocorticoid resistance with lower rates of development of features suggestive of iatrogenic Cushing's syndrome. [133][134][135][136][137][138][139][140][141][142] Time of glucocorticoid administration during the day is another important factor that likely contributes to the risk of GI-AI. Clock related genes in circulating blood cells from patients taking exogenous glucocorticoid multiple times a day were found to be abnormal, and they partially normalized after a switch to once a day administration.…”

Section: -132mentioning

confidence: 99%

“…This variation is possibly linked—among other factors—to polymorphisms of the genes encoding the glucocorticoid and mineralocorticoid receptors 14129130131132. Glucocorticoid receptor polymorphisms were reported to be associated with increased sensitivity to glucocorticoids, leading to a higher prevalence of features associated with hypercortisolism and efficacy of glucocorticoids or, by contrast, a relative glucocorticoid resistance with lower rates of development of features suggestive of iatrogenic Cushing’s syndrome 133134135136137138139140141142. Time of glucocorticoid administration during the day is another important factor that likely contributes to the risk of GI-AI.…”

Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

Glucocorticoid induced adrenal insufficiency

Prete

Bancos

2021

BMJ

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Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.

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“…Similarly, Piechaczek et al reported that no main genetic effects of the ve SNPs (rs3800373, rs9296158, rs1360780, rs9470080, and rs4713916) on depression were found [14]; Lou et al reported that rs7757037 of FKBP5 was associated with depression in Chinese systemic lupus erythematosus patients [34] in dominant model. However, this nding was inconsistent with a study among patients with coronary artery disease, indicating rs2817032 was not associated with depressive symptoms among those patients [35].…”

Section: Discussionmentioning

confidence: 98%

Associations of FKBP5 Polymorphisms and Methylation and Parenting Style With Depressive Symptoms Among Chinese Adolescents

Guo

Wang

Guo

et al. 2021

Preprint

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Background Genetic factors may interplay with environmental stressors to contribute to risks of depressive symptoms. This study aimed to investigate the association of FKBP5 polymorphisms and DNA methylation with depressive symptoms among Chinese adolescents, considering the role of parenting style. Methods This study used a nested case-control study design based on a cohort study, and the case (n = 120) and control groups (n = 118) were matched with age. Depressive symptoms, parenting style, and other demographics were measured. Fourteen potential polymorphisms and one promoter region in the FKBP5 gene were selected for genotyping and methylation analysis. Results In the adjusted models, a significant association between FKBP5 rs7757037 and depressive symptoms was found in the codominant model (AG vs. GG; adjusted odds ratio [AOR] = 2.37, 95% CI = 1.07–5.28) and dominant model (AA + AG vs. GG; AOR = 2.22, 95% CI = 1.05–4.69); rs2817032 polymorphism was associated with depressive symptoms in the codominant model and dominant model. Significant interactions between rs7757037 and the father’s parenting style were found in the codominant model (P = 0.037) and dominant model (P = 0.038), but the gene-environment interactions were not significant after correcting for multiple testing. The main and interactive effects of FKBP5 methylation status on depressive symptoms were not observed, and no significant mediations were found in the association between FKBP5 polymorphisms and depressive symptoms through the methylation mechanism. Conclusions Further studies are required to confirm the effect of FKBP5 polymorphisms and methylation as well as their interactions with parenting styles in larger samples.

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Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients

Cited by 23 publications

References 44 publications

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

Glucocorticoid induced adrenal insufficiency

Associations of FKBP5 Polymorphisms and Methylation and Parenting Style With Depressive Symptoms Among Chinese Adolescents

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