Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure
The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/12/6/834 |
| _version_ | 1797532176593453056 |
|---|---|
| author | Špela Šalamon Sebastjan Bevc Robert Ekart Radovan Hojs Uroš Potočnik |
| author_facet | Špela Šalamon Sebastjan Bevc Robert Ekart Radovan Hojs Uroš Potočnik |
| author_sort | Špela Šalamon |
| collection | DOAJ |
| description | The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near <i>GATM</i>) is more frequent in dialysis-independent CKD patients (<i>n</i> = 135, adjusted <i>p</i> = 0.020) but not dialysis-dependent kidney failure patients (<i>n</i> = 73) compared to healthy controls (<i>n</i> = 309). The allele C of intronic SNP rs4293393 (<i>UMOD</i>) is more frequent in healthy controls (adjusted <i>p</i> = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (<i>BCAS3</i>) is associated with decreased eGFRcys (adjusted <i>p</i> = 0.001) and eGFRcrea (adjusted <i>p</i> = 0.017). Our results provide further evidence of a genetic difference between dialysis-independent CKD and dialysis-dependent kidney failure, and add the <i>GATM</i> gene locus to the list of loci associated only with dialysis-independent CKD. <i>GATM</i> risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci. |
| first_indexed | 2024-03-10T10:55:24Z |
| format | Article |
| id | doaj.art-39d5a3d764f94abbb1c37a5661382fd2 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T10:55:24Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-39d5a3d764f94abbb1c37a5661382fd22023-11-21T21:52:34ZengMDPI AGGenes2073-44252021-05-0112683410.3390/genes12060834Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney FailureŠpela Šalamon0Sebastjan Bevc1Robert Ekart2Radovan Hojs3Uroš Potočnik4Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska ul. 8, 2000 Maribor, SloveniaDepartment of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, SloveniaDepartment of Internal Medicine and Department of Pharmacology, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, SloveniaDepartment of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, SloveniaCenter for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska ul. 8, 2000 Maribor, SloveniaThe ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near <i>GATM</i>) is more frequent in dialysis-independent CKD patients (<i>n</i> = 135, adjusted <i>p</i> = 0.020) but not dialysis-dependent kidney failure patients (<i>n</i> = 73) compared to healthy controls (<i>n</i> = 309). The allele C of intronic SNP rs4293393 (<i>UMOD</i>) is more frequent in healthy controls (adjusted <i>p</i> = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (<i>BCAS3</i>) is associated with decreased eGFRcys (adjusted <i>p</i> = 0.001) and eGFRcrea (adjusted <i>p</i> = 0.017). Our results provide further evidence of a genetic difference between dialysis-independent CKD and dialysis-dependent kidney failure, and add the <i>GATM</i> gene locus to the list of loci associated only with dialysis-independent CKD. <i>GATM</i> risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.https://www.mdpi.com/2073-4425/12/6/834chronic kidney disease (CKD)kidney failurers2453533rs4293393<i>GATM</i>UMOD |
| spellingShingle | Špela Šalamon Sebastjan Bevc Robert Ekart Radovan Hojs Uroš Potočnik Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure Genes chronic kidney disease (CKD) kidney failure rs2453533 rs4293393 <i>GATM</i> UMOD |
| title | Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure |
| title_full | Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure |
| title_fullStr | Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure |
| title_full_unstemmed | Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure |
| title_short | Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure |
| title_sort | polymorphism in the i gatm i locus associated with dialysis independent chronic kidney disease but not dialysis dependent kidney failure |
| topic | chronic kidney disease (CKD) kidney failure rs2453533 rs4293393 <i>GATM</i> UMOD |
| url | https://www.mdpi.com/2073-4425/12/6/834 |
| work_keys_str_mv | AT spelasalamon polymorphismintheigatmilocusassociatedwithdialysisindependentchronickidneydiseasebutnotdialysisdependentkidneyfailure AT sebastjanbevc polymorphismintheigatmilocusassociatedwithdialysisindependentchronickidneydiseasebutnotdialysisdependentkidneyfailure AT robertekart polymorphismintheigatmilocusassociatedwithdialysisindependentchronickidneydiseasebutnotdialysisdependentkidneyfailure AT radovanhojs polymorphismintheigatmilocusassociatedwithdialysisindependentchronickidneydiseasebutnotdialysisdependentkidneyfailure AT urospotocnik polymorphismintheigatmilocusassociatedwithdialysisindependentchronickidneydiseasebutnotdialysisdependentkidneyfailure |