Epistatic Interactions between CREB and CREM Variants in Affective Disorder

Chiesa, Alberto; Marsano, Agnese; Han, Changsu; Lee, Soo Jung; Patkar, Ashwin A.; Pae, Chi Un; Serretti, Alessandro

doi:10.4306/pi.2014.11.2.200

Cited by 3 publications

(1 citation statement)

References 24 publications

(37 reference statements)

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“…The purity of DNA was checked using absorbance ratio at 260/280 where the acceptable range was 1.8‐2. Three SNPs were selected: GOAT rs10096097, [ 11 ] CREB1 rs6740584, [ 58 ] and MafA rs62521874. [ 59 ] The applicant SNPs were chosen according to values of more than 5% for minor allele frequency (MAF).…”

Section: Methodsmentioning

confidence: 99%

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians

Shahin,

Shaker,

Mahmoud

2024

Archiv der Pharmazie

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Diabetes mellitus (DM) is a chronic disorder that affects nearly half a billion people around the world and causes millions of deaths annually. Treatment of diabetes or related complications represents an economic burden not only for developing countries but also for the developed ones. Hence, new efficient therapeutic and preventive strategies and screening tools are necessary. The current work aimed to assess the potential association of single nucleotide polymorphisms (SNPs) in ghrelin O‐acyltransferase (GOAT) rs10096097, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) rs6740584, and v‐maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) rs62521874 genes with type 2 DM susceptibility in Egyptians. A total of 96 patients with type 2 DM along with 72 healthy individuals participated in this study. Genotyping was executed via real‐time polymerase chain reaction (PCR), and the serum protein levels of GOAT, CREB, and MafA were measured by enzyme‐linked immunosorbent assay (ELISA). Genotyping revealed a significant association of GOAT rs10096097 and CREB1 rs6740584 SNPs with type 2 diabetes risk, with significantly higher GOAT rs10096097 G allele and CREB1 rs6740584 T allele frequencies in diabetic patients than in controls. However, insignificant association was identified between the MafA rs62521874 SNP and diabetes in the examined sample of the Egyptian residents. Serum GOAT, CREB1, and MafA protein levels did not vary significantly between diabetic and control individuals. Yet, significant variation in serum GOAT and CREB1 levels was detected between CREB1 rs6740584 genotypes within the diabetic group, with CT and TT genotype carriers showing higher levels than AA genotype patients. GOAT rs10096097 and CREB1 rs6740584, but not MafA rs62521874, SNPs are associated with type 2 diabetes risk in the studied Egyptians.

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Section: Methodsmentioning

confidence: 99%

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians

Shahin,

Shaker,

Mahmoud

2024

Archiv der Pharmazie

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The Mechanisms Underlying the Pharmacological Effects of GuiPi Decoction on Major Depressive Disorder based on Network Pharmacology and Molecular Docking

Chen

Wang

et al. 2023

CCHTS

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Background and aim: Major depressive disorder (MDD) is a common affective disorder. GuiPi decoction (GPD) is used to treat depression in China, Japan, and Korea. However, its effective ingredients and antidepressant mechanisms remain unclear. We attempted to reveal the potential mechanisms of GPD in the treatment of MDD by network pharmacology and molecular docking. In addition, we conducted an enzymatic activity assay to validate the results of molecular docking. Methods: GPD-related compounds and targets, MDD-related targets were retrieved from databases and literature. The herb-compound-target network was constructed by Cytoscape. The protein-protein interaction network was built using STRING database to find key targets of GPD on MDD. Enrichment analysis of shared targets were analyzed by MetaCore database to obtain the potential pathway and biological process of GPD on MDD. The main active compounds treating for MDD were screened by molecular docking. The PDE4s inhibitors were screened and verified by an enzyme activity assay. Results: GPD contained 1222 ingredients and 190 potential targets for anti-MDD. Possible biological processes regulated by GPD were neurophysiological processes, blood vessel morphogenesis, cAMP responsive element modulator (CREM) pathway, and androgen receptor (AR) signaling crosstalk in MDD. Potential pathways in MDD associated with GPD include neurotransmission, cell differentiation, androgen signaling, and estrogen signaling. Fumarine, m-cresol, quercetin, beta-sitosterol, fumarine, taraxasterol, and lupeol in GPD may be the targets of SLC6A4, monoamine oxidase A (MAOA), DRD2, OPRM1, HTR3A, albumin (ALB), and NTRK1, respectively. The IC50 values of trifolin targeting phosphodiesterase (PDE)4A and girinimbine targeting PDE4B1 were 73.79 μM and 31.86 μM, respectively. The IC50 values of girinimbine and benzo[a]carbazole on PDE4B2 were 51.62 μM and 94.61 μM, respectively. Conclusion: Different compounds in GPD may target the same protein, and the same component in GPD can target multiple targets. These results suggest that the effects of GPD on MDD are holistic and systematic, unlike the pattern of one drug-one target.

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Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

Porcelli

Pae

Han

et al. 2014

Psychiatry Investig

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ObjectiveThe present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders.MethodsOne hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy.ResultsThe rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects.ConclusionOur findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations.

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Epistatic Interactions between CREB and CREM Variants in Affective Disorder

Cited by 3 publications

References 24 publications

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians

The Mechanisms Underlying the Pharmacological Effects of GuiPi Decoction on Major Depressive Disorder based on Network Pharmacology and Molecular Docking

Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

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