T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00084960" target="_blank" >RIV/00023001:_____/24:00084960 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00136589 RIV/00216208:11110/24:10483210 RIV/65269705:_____/24:00080247 RIV/00159816:_____/24:00080247

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S037811192400605X?via%3Dihub#ak005" target="_blank" >https://www.sciencedirect.com/science/article/pii/S037811192400605X?via%3Dihub#ak005</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2024.148724" target="_blank" >10.1016/j.gene.2024.148724</a>

Jazyk výsledku

angličtina

Název v původním jazyce

T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects

Popis výsledku v původním jazyce

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P &lt; 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P &lt; 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

Název v anglickém jazyce

T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects

Popis výsledku anglicky

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P &lt; 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P &lt; 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Gene

ISSN

0378-1119

e-ISSN

1879-0038

Svazek periodika

927

Číslo periodika v rámci svazku

November 15

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

"art. no. 148724"

Kód UT WoS článku

001262948200001

EID výsledku v databázi Scopus

2-s2.0-85196798829