Genetic risk score in patients with the APOE2/E2 genotype as a
predictor of familial dysbetalipoproteinemia

J 2024

Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia

SATNY, Martin; Veronika TODOROVOVA; Tereza ALTSCHMIEDOVA; Jaroslav A HUBACEK; Lucie DLOUHA et. al.

Základní údaje

Originální název

Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia

Autoři

SATNY, Martin; Veronika TODOROVOVA; Tereza ALTSCHMIEDOVA; Jaroslav A HUBACEK; Lucie DLOUHA; Vera LANSKA; Vladimír SOŠKA; Ondřej KYSELÁK; Tomáš FREIBERGER ; Martin BOBÁK a Michal VRABLIK

Vydání

Journal of Clinical Lipidology, NEW YORK, ELSEVIER SCIENCE INC, 2024, 1933-2874

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30218 General and internal medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.600

Kód RIV

RIV/00216224:14110/24:00135522

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1016/j.jacl.2023.11.010

UT WoS

001239945500003

EID Scopus

2-s2.0-85178638779

Klíčová slova anglicky

Familial dysbetalipoproteinemia; Cardiovascular risk; Polymorphism; Genetic risk score

Štítky

14110114, 14110116, rivok

Příznaky

Recenzováno

Změněno: 9. 7. 2024 11:44, Mgr. Tereza Miškechová

Anotace

V originále

Background Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. Methods One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. Results Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (OR 3.58, CI: 1.78–7.18, P < 0.0005). Conclusions We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.

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

Přiložené soubory

Genetic_risk_score_in_patients_with_the_APOE2_E2_genotype_as_a_predictor_of_familial_dysbetalipoproteinemia_dmeljbco.pdf

Genetic_risk_score_in_patients_with_the_APOE2_E2_genotype_as_a_predictor_of_familial_dysbetalipoproteinemia.pdf

Citovat

SATNY, Martin; Veronika TODOROVOVA; Tereza ALTSCHMIEDOVA; Jaroslav A HUBACEK; Lucie DLOUHA; Vera LANSKA; Vladimír SOŠKA; Ondřej KYSELÁK; Tomáš FREIBERGER; Martin BOBÁK a Michal VRABLIK. Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia. Journal of Clinical Lipidology. NEW YORK: ELSEVIER SCIENCE INC, 2024, roč. 18, č. 2, s. "e230"-"e237", 8 s. ISSN 1933-2874. Dostupné z: https://doi.org/10.1016/j.jacl.2023.11.010.

@article{2374298,
   author = {Satny, Martin and Todorovova, Veronika and Altschmiedova, Tereza and Hubacek, Jaroslav A and Dlouha, Lucie and Lanska, Vera and Soška, Vladimír and Kyselák, Ondřej and Freiberger, Tomáš and Bobák, Martin and Vrablik, Michal},
   article_location = {NEW YORK},
   article_number = {2},
   doi = {https://doi.org/10.1016/j.jacl.2023.11.010},
   keywords = {Familial dysbetalipoproteinemia; Cardiovascular risk; Polymorphism; Genetic risk score},
   language = {eng},
   issn = {1933-2874},
   journal = {Journal of Clinical Lipidology},
   title = {Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia},
   url = {https://www.sciencedirect.com/science/article/pii/S1933287423003422?via%3Dihub},
   volume = {18},
   year = {2024}
}

TY  - JOUR
ID  - 2374298
AU  - Satny, Martin - Todorovova, Veronika - Altschmiedova, Tereza - Hubacek, Jaroslav A - Dlouha, Lucie - Lanska, Vera - Soška, Vladimír - Kyselák, Ondřej - Freiberger, Tomáš - Bobák, Martin - Vrablik, Michal
PY  - 2024
TI  - Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia
JF  - Journal of Clinical Lipidology
VL  - 18
IS  - 2
SP  - "e230"-"e237"
EP  - "e230"-"e237"
PB  - ELSEVIER SCIENCE INC
SN  - 19332874
KW  - Familial dysbetalipoproteinemia
KW  - Cardiovascular risk
KW  - Polymorphism
KW  - Genetic risk score
UR  - https://www.sciencedirect.com/science/article/pii/S1933287423003422?via%3Dihub
N2  - Background Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. Methods One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. Results Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (OR 3.58, CI: 1.78–7.18, P < 0.0005). Conclusions We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.
ER  -

SATNY, Martin; Veronika TODOROVOVA; Tereza ALTSCHMIEDOVA; Jaroslav A HUBACEK; Lucie DLOUHA; Vera LANSKA; Vladimír SOŠKA; Ondřej KYSELÁK; Tomáš FREIBERGER; Martin BOBÁK a Michal VRABLIK. Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia. \textit{Journal of Clinical Lipidology}. NEW YORK: ELSEVIER SCIENCE INC, 2024, roč.~18, č.~2, s.~''e230''-''e237'', 8 s. ISSN~1933-2874. Dostupné z: https://doi.org/10.1016/j.jacl.2023.11.010.

Přehled o publikaci