Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements
Abstract The connection between chronic kidney disease (CKD) and acute kidney injury (AKI) is becoming more widely acknowledged, as the two conditions probably exacerbate one other. The purpose of the present study was to evaluate the circulating levels of fibroblast growth factor 23 (FGF23), αKloth...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-01-01
|
| Series: | The Egyptian Journal of Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43162-024-00391-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544311982784512 |
|---|---|
| author | Mohammed H. Hassan Tahia H. Saleem Ahmed Alamir Mahmoud Abdallah Marwa Abdelhady Doha Abd-Elraheem Salama Abdelrahman A. Elsaied Abdallah Elaiw Mohammed Abdelkader Ahmed Hashim |
| author_facet | Mohammed H. Hassan Tahia H. Saleem Ahmed Alamir Mahmoud Abdallah Marwa Abdelhady Doha Abd-Elraheem Salama Abdelrahman A. Elsaied Abdallah Elaiw Mohammed Abdelkader Ahmed Hashim |
| author_sort | Mohammed H. Hassan |
| collection | DOAJ |
| description | Abstract The connection between chronic kidney disease (CKD) and acute kidney injury (AKI) is becoming more widely acknowledged, as the two conditions probably exacerbate one other. The purpose of the present study was to evaluate the circulating levels of fibroblast growth factor 23 (FGF23), αKlotho, and mircoRNA-126 (miR-126) and to explore the possible genetic role of single nucleotide polymorphisms (SNPs) in the klotho G-395A (rs1207568), C1818T (rs564481), and wnt signaling pathway AXIN-1 C > T (rs9921222) in AKI and CKD patients and their relation to progression of kidney disease and dialysis necessity. In this case–control study, there were 50 AKI patients, 100 CKD patients, and 50 healthy controls. ELISA assay kits were utilized to measure the plasma concentrations of FGF23 and α klotho, while reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression levels of miR-126. Using conventional PCR methods, rs1207568, rs564481 and rs9921222 SNPs were genetically analyzed. Patients with AKI and CKD had significantly higher median FGF23 levels than controls (P < 0.05), with the AKI group showing much higher levels than the CKD patients (P < 0.05). Patients with AKI and CKD had significantly lower median αKlotho levels than controls (P < 0.001). When CKD patients were compared to controls and AKI patients, the expression levels of miR-126 were significantly greater, while significantly lower in AKI patients compared to controls, (P < 0.05). AKI and CKD patients had a significantly greater frequency of GG genotype of rs1207568 than the control group (< 0.001, and = 0.021 respectively). However, for klotho rs564481, all participants had CT genotype. In the CKD group compared to controls, rs9921222 SNP revealed a considerably greater frequency of mutant heterozygous CT genotype with a significantly lower wild CC genotype, P = < 0.001. Area under the curve (AUC) value of 0.638 for miR-126 expression levels indicate modest efficacy in identifying dialysis necessity among AKI patients. While miR-126 and plasma FGF23 expression levels among CKD patients demonstrated high efficacy, with AUC values of 0.924 and 0.845, respectively. αKlotho's AUC of 0.786 indicated a moderate level of discriminatory ability. AKI and CKD may be associated with disrupted expression levels of FGF23, αKlotho, and miR-126, which may serve as possible biomarkers for CKD patients requiring dialysis. An increased risk of developing CKD was shown to be associated with the GG genotype of the Klotho rs1207568 SNP and the CT genotype of the wnt signaling pathway rs9921222 SNP. |
| format | Article |
| id | doaj-art-c027e3a107554c9ea9e10dfd8cdfeeed |
| institution | Kabale University |
| issn | 2090-9098 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | The Egyptian Journal of Internal Medicine |
| spelling | doaj-art-c027e3a107554c9ea9e10dfd8cdfeeed2025-01-12T12:40:28ZengSpringerOpenThe Egyptian Journal of Internal Medicine2090-90982025-01-0137111710.1186/s43162-024-00391-9Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirementsMohammed H. Hassan0Tahia H. Saleem1Ahmed Alamir Mahmoud Abdallah2Marwa Abdelhady3Doha Abd-Elraheem Salama4Abdelrahman A. Elsaied5Abdallah Elaiw Mohammed6Abdelkader Ahmed Hashim7Department of Medical Biochemistry, Faculty of Medicine, South Valley UniversityDepartment of Medical Biochemistry, Faculty of Medicine, Assiut UniversityDepartment of Medical Biochemistry, Faculty of Medicine, Sohag UniversityDepartment of Internal Medicine, Faculty of Medicine, Luxor UniversityDepartment of Medical Biochemistry, Faculty of Medicine, South Valley UniversityDepartment of Clinical and Chemical Pathology, Faculty of Medicine, South Valley UniversityDepartment of Clinical and Chemical Pathology, Faculty of Medicine, South Valley UniversityDepartment of Internal Medicine (Nephrology Division), Faculty of Medicine, South Valley UniversityAbstract The connection between chronic kidney disease (CKD) and acute kidney injury (AKI) is becoming more widely acknowledged, as the two conditions probably exacerbate one other. The purpose of the present study was to evaluate the circulating levels of fibroblast growth factor 23 (FGF23), αKlotho, and mircoRNA-126 (miR-126) and to explore the possible genetic role of single nucleotide polymorphisms (SNPs) in the klotho G-395A (rs1207568), C1818T (rs564481), and wnt signaling pathway AXIN-1 C > T (rs9921222) in AKI and CKD patients and their relation to progression of kidney disease and dialysis necessity. In this case–control study, there were 50 AKI patients, 100 CKD patients, and 50 healthy controls. ELISA assay kits were utilized to measure the plasma concentrations of FGF23 and α klotho, while reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression levels of miR-126. Using conventional PCR methods, rs1207568, rs564481 and rs9921222 SNPs were genetically analyzed. Patients with AKI and CKD had significantly higher median FGF23 levels than controls (P < 0.05), with the AKI group showing much higher levels than the CKD patients (P < 0.05). Patients with AKI and CKD had significantly lower median αKlotho levels than controls (P < 0.001). When CKD patients were compared to controls and AKI patients, the expression levels of miR-126 were significantly greater, while significantly lower in AKI patients compared to controls, (P < 0.05). AKI and CKD patients had a significantly greater frequency of GG genotype of rs1207568 than the control group (< 0.001, and = 0.021 respectively). However, for klotho rs564481, all participants had CT genotype. In the CKD group compared to controls, rs9921222 SNP revealed a considerably greater frequency of mutant heterozygous CT genotype with a significantly lower wild CC genotype, P = < 0.001. Area under the curve (AUC) value of 0.638 for miR-126 expression levels indicate modest efficacy in identifying dialysis necessity among AKI patients. While miR-126 and plasma FGF23 expression levels among CKD patients demonstrated high efficacy, with AUC values of 0.924 and 0.845, respectively. αKlotho's AUC of 0.786 indicated a moderate level of discriminatory ability. AKI and CKD may be associated with disrupted expression levels of FGF23, αKlotho, and miR-126, which may serve as possible biomarkers for CKD patients requiring dialysis. An increased risk of developing CKD was shown to be associated with the GG genotype of the Klotho rs1207568 SNP and the CT genotype of the wnt signaling pathway rs9921222 SNP.https://doi.org/10.1186/s43162-024-00391-9Fibroblast growth factor 23αKlothoMicroRNA-126Acute kidney injury (AKI)Chronic kidney disease (CKD)Polymerase chain reaction (PCR) |
| spellingShingle | Mohammed H. Hassan Tahia H. Saleem Ahmed Alamir Mahmoud Abdallah Marwa Abdelhady Doha Abd-Elraheem Salama Abdelrahman A. Elsaied Abdallah Elaiw Mohammed Abdelkader Ahmed Hashim Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements The Egyptian Journal of Internal Medicine Fibroblast growth factor 23 αKlotho MicroRNA-126 Acute kidney injury (AKI) Chronic kidney disease (CKD) Polymerase chain reaction (PCR) |
| title | Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements |
| title_full | Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements |
| title_fullStr | Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements |
| title_full_unstemmed | Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements |
| title_short | Expression profile of FGF23, alpha klotho, microRNA-126, and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases: relation to dialysis requirements |
| title_sort | expression profile of fgf23 alpha klotho microrna 126 and wnt signaling pathway gene polymorphism in patients with acute or chronic kidney diseases relation to dialysis requirements |
| topic | Fibroblast growth factor 23 αKlotho MicroRNA-126 Acute kidney injury (AKI) Chronic kidney disease (CKD) Polymerase chain reaction (PCR) |
| url | https://doi.org/10.1186/s43162-024-00391-9 |
| work_keys_str_mv | AT mohammedhhassan expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT tahiahsaleem expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT ahmedalamirmahmoudabdallah expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT marwaabdelhady expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT dohaabdelraheemsalama expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT abdelrahmanaelsaied expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT abdallahelaiwmohammed expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements AT abdelkaderahmedhashim expressionprofileoffgf23alphaklothomicrorna126andwntsignalingpathwaygenepolymorphisminpatientswithacuteorchronickidneydiseasesrelationtodialysisrequirements |