-
Je něco špatně v tomto záznamu ?
Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia
M. Satny, V. Todorovova, T. Altschmiedova, JA. Hubacek, L. Dlouha, V. Lanska, V. Soska, O. Kyselak, T. Freiberger, M. Bobak, M. Vrablik
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- apolipoprotein E2 * genetika MeSH
- apolipoproteiny E genetika MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genetické rizikové skóre MeSH
- genotyp * MeSH
- hyperlipoproteinemie typ III genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 (odds ratio (OR) 3.58, 95% confidence interva (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.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24014567
- 003
- CZ-PrNML
- 005
- 20240905134109.0
- 007
- ta
- 008
- 240725s2024 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.jacl.2023.11.010 $2 doi
- 035 __
- $a (PubMed)38044203
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Satny, Martin $u 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik). Electronic address: martin.satny@vfn.cz
- 245 10
- $a Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia / $c M. Satny, V. Todorovova, T. Altschmiedova, JA. Hubacek, L. Dlouha, V. Lanska, V. Soska, O. Kyselak, T. Freiberger, M. Bobak, M. Vrablik
- 520 9_
- $a 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 (odds ratio (OR) 3.58, 95% confidence interva (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.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a jednonukleotidový polymorfismus $7 D020641
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 12
- $a apolipoprotein E2 $x genetika $7 D053329
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a lidé středního věku $7 D008875
- 650 12
- $a genotyp $7 D005838
- 650 12
- $a genetická predispozice k nemoci $7 D020022
- 650 _2
- $a hyperlipoproteinemie typ III $x genetika $7 D006952
- 650 _2
- $a rizikové faktory $7 D012307
- 650 _2
- $a studie případů a kontrol $7 D016022
- 650 _2
- $a apolipoproteiny E $x genetika $7 D001057
- 650 _2
- $a genetické rizikové skóre $7 D000096442
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Todorovova, Veronika $u 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik)
- 700 1_
- $a Altschmiedova, Tereza $u 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik)
- 700 1_
- $a Hubacek, Jaroslav A $u 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik); Centre of Experimental Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic (Drs Hubacek and Lanska)
- 700 1_
- $a Dlouha, Lucie $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic (Dr Dlouha)
- 700 1_
- $a Lanska, Vera $u Centre of Experimental Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic (Drs Hubacek and Lanska)
- 700 1_
- $a Soska, Vladimir $u Clinical Biochemistry Department, St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak); 2nd Internal Department, Faculty of Medicine Masaryk University and St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak)
- 700 1_
- $a Kyselak, Ondrej $u Clinical Biochemistry Department, St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak); 2nd Internal Department, Faculty of Medicine Masaryk University and St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak)
- 700 1_
- $a Freiberger, Tomas $u Centre for Cardiovascular Surgery and Transplantation, Brno, and Medical Faculty, Masaryk University, Brno, Czech Republic (Dr Freiberger)
- 700 1_
- $a Bobak, Martin $u Institute of Epidemiology and Health Care, University College London, London WC1E 7HB, United Kingdom, and Medical Faculty, Masaryk University, Brno, Czech Republic (Dr Bobak)
- 700 1_
- $a Vrablik, Michal $u 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik)
- 773 0_
- $w MED00166943 $t Journal of clinical lipidology $x 1933-2874 $g Roč. 18, č. 2 (2024), s. e230-e237
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38044203 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240725 $b ABA008
- 991 __
- $a 20240905134103 $b ABA008
- 999 __
- $a ok $b bmc $g 2143999 $s 1226433
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 18 $c 2 $d e230-e237 $e 20231123 $i 1933-2874 $m Journal of clinical lipidology $n J Clin Lipidol $x MED00166943
- LZP __
- $a Pubmed-20240725
