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

J 2024

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

GALUŠKA, David; Lukáš PÁCAL; Katarína CHALÁSOVÁ; Petra DIVÁCKÁ; Jitka ŘEHOŘOVÁ et al.

Základní údaje

Originální název

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

Autoři

GALUŠKA, David ; Lukáš PÁCAL; Katarína CHALÁSOVÁ; Petra DIVÁCKÁ; Jitka ŘEHOŘOVÁ; Jan SVOJANOVSKÝ; Jaroslav A. HUBACEK; Vera LANSKA a Kateřina KAŇKOVÁ

Vydání

Gene, Amsterdam, Elsevier Science, 2024, 0378-1119

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30101 Human genetics

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00136589

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Genetic risk score; Diabetic kidney disease; Diabetes mellitus; Genetic predisposition; Single nucleotide polymorphism

Štítky

14110512, 14110518, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 2. 2025 09:21, Mgr. Tereza Miškechová

Anotace

V originále

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 < 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 < 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.

Návaznosti

LX22NPO5104, projekt VaV

Název: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění (Akronym: CarDia)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut pro léčbu metabolických a kardiovaskulárních onemocnění, 5.1 EXCELES

MUNI/A/1587/2023, interní kód MU

Název: Patofyziologie vybraných komplexních nemocí od molekulární do systémovou úroveň

Investor: Masarykova univerzita, Patofyziologie vybraných komplexních nemocí od molekulární do systémovou úroveň

NV18-01-00046, projekt VaV

Název: Genetické skóre v predikci rizika diabetu a jeho komplikací

Investor: Ministerstvo zdravotnictví ČR, Genetické skóre v predikci rizika diabetu a jeho komplikací

Přiložené soubory

T2DM_CKD_genetic_risk_scores_and_the_progression_of_diabetic_kidney_disease_in_T2DM_subjects.pdf

Citovat

GALUŠKA, David; Lukáš PÁCAL; Katarína CHALÁSOVÁ; Petra DIVÁCKÁ; Jitka ŘEHOŘOVÁ; Jan SVOJANOVSKÝ; Jaroslav A. HUBACEK; Vera LANSKA a Kateřina KAŇKOVÁ. T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects. Gene. Amsterdam: Elsevier Science, 2024, roč. 927, November 2024, s. 1-8. ISSN 0378-1119. Dostupné z: https://doi.org/10.1016/j.gene.2024.148724.

@article{2419841,
   author = {Galuška, David and Pácal, Lukáš and Chalásová, Katarína and Divácká, Petra and Řehořová, Jitka and Svojanovský, Jan and Hubacek, Jaroslav A. and Lanska, Vera and Kaňková, Kateřina},
   article_location = {Amsterdam},
   article_number = {November 2024},
   doi = {https://doi.org/10.1016/j.gene.2024.148724},
   keywords = {Genetic risk score; Diabetic kidney disease; Diabetes mellitus; Genetic predisposition; Single nucleotide polymorphism},
   language = {eng},
   issn = {0378-1119},
   journal = {Gene},
   title = {T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects},
   url = {https://www.sciencedirect.com/science/article/pii/S037811192400605X?via%3Dihub},
   volume = {927},
   year = {2024}
}

TY  - JOUR
ID  - 2419841
AU  - Galuška, David - Pácal, Lukáš - Chalásová, Katarína - Divácká, Petra - Řehořová, Jitka - Svojanovský, Jan - Hubacek, Jaroslav A. - Lanska, Vera - Kaňková, Kateřina
PY  - 2024
TI  - T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects
JF  - Gene
VL  - 927
IS  - November 2024
SP  - 1-8
EP  - 1-8
PB  - Elsevier Science
SN  - 03781119
KW  - Genetic risk score
KW  - Diabetic kidney disease
KW  - Diabetes mellitus
KW  - Genetic predisposition
KW  - Single nucleotide polymorphism
UR  - https://www.sciencedirect.com/science/article/pii/S037811192400605X?via%3Dihub
N2  - 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 < 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 < 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.
ER  -

GALUŠKA, David; Lukáš PÁCAL; Katarína CHALÁSOVÁ; Petra DIVÁCKÁ; Jitka ŘEHOŘOVÁ; Jan SVOJANOVSKÝ; Jaroslav A. HUBACEK; Vera LANSKA a Kateřina KAŇKOVÁ. T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects. \textit{Gene}. Amsterdam: Elsevier Science, 2024, roč.~927, November 2024, s.~1-8. ISSN~0378-1119. Dostupné z: https://doi.org/10.1016/j.gene.2024.148724.

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