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The association between genetic variant ZNF259 and decreased kidney function in the diabetic patients
Session:
Posters 1 - Écran 2 - Doença Coronária
Speaker:
Andreia Pereira
Congress:
CPC 2019
Topic:
E. Coronary Artery Disease, Acute Coronary Syndromes, Acute Cardiac Care
Theme:
12. Coronary Artery Disease (Chronic)
Subtheme:
12.5 Coronary Artery Disease – Prevention
Session Type:
Posters
FP Number:
---
Authors:
Andreia Pereira; Maria Isabel Mendonça; Joao Adriano Sousa; Flávio Mendonça; Micaela Rodrigues Neto; Joel Monteiro; Ana Célia Sousa; Eva Henriques; Sónia Freitas; Ana Isabel; Ilídio Ornelas; A. Drumond de Freitas; Roberto Palma dos Reis
Abstract
<p>Type 2 Diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, it remains unclear whether this association is only causal. Genetic variants are inherited independent of potential confounding factors and represent a lifetime exposure.</p> <p><strong>Aim:</strong> Investigate whether the reduction of GFR is a direct consequence of T2D or there are other genetic mechanisms involved in the pathophysiology of the evolution to chronic kidney disease.</p> <p><strong>Methods:</strong> Cross-sectional study with a total of 2579 individuals was performed, of which 735 patients had T2D. Subjects were classified as ´diabetic´ if they were taking oral anti-diabetic medication or insulin or if their fasting plasma glucose was higher than 7.0 mmol/l or 126 mg/dl. Within the diabetic group, we considered those with (n=63) and without (n=627) decreased GFR. GFR was calculated through the Cockcroft and Gault formula and decreased GFR was defined as GFR<60 ml/min/1.73m<sup>2</sup>. Twenty-four genetic variants associated with T2D, metabolic syndrome, dyslipidemia and hypertension were investigated for its impact on GFR, namely: MTHFR 677 and 1298; MTHFD1L; PON 55, 192 and 108; ATIR A/C; AGT M235T; ACE I/D; TCF7L2; SLC30A8; MC4R; ADIPOQ; FTO; TAS2R50; HNF4A; IGF2BP2; PPARG; PCSK9; KIF6; ZNF259; LPA; APOE; PSRS1. Risk factors for decreased GFR were also evaluated (essential hypertension, glycaemia >120 mg/ml, dyslipidemia, alcohol consumption, CAD diagnosis). A logistic regression was performed firstly with the risk factors solely; and secondly adding the genetic variants in order to evaluate the independent predictors of progression to renal failure in T2D.</p> <p><strong>Results:</strong> After the first multivariate logistic regression with all the risk factors for decreased GFR, only CAD remained in the equation, showing to be an independent risk factor for progression to renal failure, in T2D (OR=4.17; 95%CI: 1.64-10.59; p=0.003). In the second logistic regression, including risk factors and the genetic variants, only ZNF259 rs964184 showed an independent and significant association with the risk of decreased GFR (OR=3.03; 95%CI: 1.06-8.70; p=0.039).</p> <p><strong>Conclusion</strong>: This study shows that the variant ZNF259 rs964184 is associated with decreased kidney function, independently of other risk factors. This finding needs further investigation to clarify the genetic mechanism behind the association of rs964184 with decreased GFR, in Type 2 diabetes.</p>
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