Genetic aspects of decreased low-density lipoprotein cholesterol values
Aim. To study genetic causes of decreased low-density lipoprotein cholesterol (LDL-C) in Russian patients.Material and methods. The study included the following Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) participants: individuals with LD...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
«SILICEA-POLIGRAF» LLC
2023-12-01
|
| Series: | Кардиоваскулярная терапия и профилактика |
| Subjects: | |
| Online Access: | https://cardiovascular.elpub.ru/jour/article/view/3846 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849699403882823680 |
|---|---|
| author | A. N. Meshkov A. I. Ershova A. V. Kiseleva V. I. Mikhailina S. A. Smetnev А. G. Soplenkova V. A. Kutsenko Е. A. Sotnikova Yu. V. Vyatkin A. A. Zharikova M. Zaichenoka V. E. Ramensky O. P. Skirko M. S. Pokrovskaya O. A. Litinskaya S. A. Shalnova O. M. Drapkina |
| author_facet | A. N. Meshkov A. I. Ershova A. V. Kiseleva V. I. Mikhailina S. A. Smetnev А. G. Soplenkova V. A. Kutsenko Е. A. Sotnikova Yu. V. Vyatkin A. A. Zharikova M. Zaichenoka V. E. Ramensky O. P. Skirko M. S. Pokrovskaya O. A. Litinskaya S. A. Shalnova O. M. Drapkina |
| author_sort | A. N. Meshkov |
| collection | DOAJ |
| description | Aim. To study genetic causes of decreased low-density lipoprotein cholesterol (LDL-C) in Russian patients.Material and methods. The study included the following Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) participants: individuals with LDL-C<5th percentile, taking into account sex and age (n=52), who underwent targeted sequencing of protein-coding regions of 6 genes (APOB, PCSK9, MTTP, ANGPTL3, SAR1B, APOC3) and determination of the genetic risk score (GRS) for hypercholesterolemia; and a representative sample of the Ivanovo region population (ESSEIvanovo, n=1667), for which only GRS was determined. Genetic testing was performed using next generation sequencing.Results. In 10 (19,2%) of 52 participants with decreased LDL-C levels, the following rare variants potentially associated with hypocholesterolemia were identified: 8 — leading to a premature termination codon in the APOB gene, 1 — leading to a premature termination codon in the APOC3 gene and 1 missense variant in the PCSK9 gene. Of the 10 identified variants, 6 are described by us for the first time. GRS in the LDL-C group (0,27±0,25) was significantly lower than in the ESSE-Ivanovo population sample (0,43±0,27) (p=4,7×10-06).Conclusion. Genetic reasons explain decreased LDL-C levels (<5th percentile) in 32,7% of patients, of which only monogenic variants were identified in 13,5%, a combination of monogenic and polygenic hypocholesterolemia — in 5,7%, and polygenic hypocholesterolemia — in 13,5%. |
| format | Article |
| id | doaj-art-058dd6f74572472ebdc94e25fbded0d9 |
| institution | DOAJ |
| issn | 1728-8800 2619-0125 |
| language | Russian |
| publishDate | 2023-12-01 |
| publisher | «SILICEA-POLIGRAF» LLC |
| record_format | Article |
| series | Кардиоваскулярная терапия и профилактика |
| spelling | doaj-art-058dd6f74572472ebdc94e25fbded0d92025-08-20T03:18:35Zrus«SILICEA-POLIGRAF» LLCКардиоваскулярная терапия и профилактика1728-88002619-01252023-12-01221210.15829/1728-8800-2023-38462843Genetic aspects of decreased low-density lipoprotein cholesterol valuesA. N. Meshkov0A. I. Ershova1A. V. Kiseleva2V. I. Mikhailina3S. A. Smetnev4А. G. Soplenkova5V. A. Kutsenko6Е. A. Sotnikova7Yu. V. Vyatkin8A. A. Zharikova9M. Zaichenoka10V. E. Ramensky11O. P. Skirko12M. S. Pokrovskaya13O. A. Litinskaya14S. A. Shalnova15O. M. Drapkina16National Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive Medicine; Lomonosov Moscow State UniversityNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive Medicine; Lomonosov Moscow State UniversityNational Medical Research Center for Therapy and Preventive Medicine; Lomonosov Moscow State UniversityMoscow Institute of Physics and TechnologyNational Medical Research Center for Therapy and Preventive Medicine; Lomonosov Moscow State UniversityNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineNational Medical Research Center for Therapy and Preventive MedicineAim. To study genetic causes of decreased low-density lipoprotein cholesterol (LDL-C) in Russian patients.Material and methods. The study included the following Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) participants: individuals with LDL-C<5th percentile, taking into account sex and age (n=52), who underwent targeted sequencing of protein-coding regions of 6 genes (APOB, PCSK9, MTTP, ANGPTL3, SAR1B, APOC3) and determination of the genetic risk score (GRS) for hypercholesterolemia; and a representative sample of the Ivanovo region population (ESSEIvanovo, n=1667), for which only GRS was determined. Genetic testing was performed using next generation sequencing.Results. In 10 (19,2%) of 52 participants with decreased LDL-C levels, the following rare variants potentially associated with hypocholesterolemia were identified: 8 — leading to a premature termination codon in the APOB gene, 1 — leading to a premature termination codon in the APOC3 gene and 1 missense variant in the PCSK9 gene. Of the 10 identified variants, 6 are described by us for the first time. GRS in the LDL-C group (0,27±0,25) was significantly lower than in the ESSE-Ivanovo population sample (0,43±0,27) (p=4,7×10-06).Conclusion. Genetic reasons explain decreased LDL-C levels (<5th percentile) in 32,7% of patients, of which only monogenic variants were identified in 13,5%, a combination of monogenic and polygenic hypocholesterolemia — in 5,7%, and polygenic hypocholesterolemia — in 13,5%.https://cardiovascular.elpub.ru/jour/article/view/3846apobapoc3pcsk9hypocholesterolemialow-density lipoprotein cholesterolgenetic risk score |
| spellingShingle | A. N. Meshkov A. I. Ershova A. V. Kiseleva V. I. Mikhailina S. A. Smetnev А. G. Soplenkova V. A. Kutsenko Е. A. Sotnikova Yu. V. Vyatkin A. A. Zharikova M. Zaichenoka V. E. Ramensky O. P. Skirko M. S. Pokrovskaya O. A. Litinskaya S. A. Shalnova O. M. Drapkina Genetic aspects of decreased low-density lipoprotein cholesterol values Кардиоваскулярная терапия и профилактика apob apoc3 pcsk9 hypocholesterolemia low-density lipoprotein cholesterol genetic risk score |
| title | Genetic aspects of decreased low-density lipoprotein cholesterol values |
| title_full | Genetic aspects of decreased low-density lipoprotein cholesterol values |
| title_fullStr | Genetic aspects of decreased low-density lipoprotein cholesterol values |
| title_full_unstemmed | Genetic aspects of decreased low-density lipoprotein cholesterol values |
| title_short | Genetic aspects of decreased low-density lipoprotein cholesterol values |
| title_sort | genetic aspects of decreased low density lipoprotein cholesterol values |
| topic | apob apoc3 pcsk9 hypocholesterolemia low-density lipoprotein cholesterol genetic risk score |
| url | https://cardiovascular.elpub.ru/jour/article/view/3846 |
| work_keys_str_mv | AT anmeshkov geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT aiershova geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT avkiseleva geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT vimikhailina geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT sasmetnev geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT agsoplenkova geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT vakutsenko geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT easotnikova geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT yuvvyatkin geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT aazharikova geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT mzaichenoka geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT veramensky geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT opskirko geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT mspokrovskaya geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT oalitinskaya geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT sashalnova geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues AT omdrapkina geneticaspectsofdecreasedlowdensitylipoproteincholesterolvalues |