Abstract: SA-PO419
Effects of the GLUT1 A-2841T Polymorphism on Proteinuria in CKD Patients Prior to the Onset of ESRD
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Ilic, Ljubomir M., University of Florida College of Medicine Jacksonville, Jacksonville, Florida, United States
- Tfirn, Ian, UF Health, Jacksonville, Florida, United States
- Smotherman, Carmen, University of Florida, Jacksonville, Florida, United States
- Heilig, Charles W., University of Florida, Jacksonville, Florida, United States
Background
The potential role of selected Glucose transporter 1 (GLUT1) single nucleotide polymorphisms (SNP)s in the pathogenesis of diabetic kidney disease has previously been published in human studies, with certain polymorphisms conferring a higher risk of nephropathy. We studied the effects of the GLUT1 A-2841T SNP in the promoter region on proteinuria in chronic kidney disease (CKD) patients prior to onset of their end-stage renal disease (ESRD).
Methods
This was a prospective cohort study of 127 ESRD patients whose GLUT1 A-2841T genotype was determined from their blood specimen and classified as: AA, AT or TT with the T polymorphism present in none, one or both alleles, respectively. Proteinuria was assessed by the highest protein to creatinine ratio within the 6-month period prior to ESRD onset, provided there was no sign of acute kidney injury. Covariates collected were patient age, race/ethnicity, gender, ESRD cause and date of onset as documented by their chronic dialysis unit, left ventricular ejection fraction <40%, smoking status, and presence of coronary/peripheral arterial disease. The gene analysis was performed by the UF Center for Biotechnology. Protein to creatinine ratio results were available in 78 patients. ESRD causes were categorized as type 2 or 1 diabetes mellitus, hypertension, polycystic kidney disease, glomerulonephritis or primary nephrotic syndromes, and other. The data were analyzed using Fisher’s exact tests and multiple regression.
Results
The distribution of genotypes does not vary among the ESRD causes (p=0.54), but differs among the race/ethnicities (p=0.0002), with the TT genotype present in 50%(4/8), 7.7% (8/104), 10%(1/10) and 40%(2/5) of Hispanic, black, white and American Indian/other patients, respectively. Adjusting for the ESRD cause, the TT genotype is associated with 5.73 g/g more proteinuria than AA (95%CI 2.9,8.5;p=0.0001). The AT genotype is associated with 0.71 g/g more proteinuria than AA, but the results are not significant.
Conclusion
Proteinuria in CKD patients tends to increase with a single A to T allele change at the -2841 position of the GLUT1 gene and becomes very significant with A to T changes in both alleles, with the results applicable to all ESRD causes.
Funding
- Commercial Support – Dialysis Clinic, Inc.