Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of sudden cardiac death
- Authors: Kachnov VA1, Kryukov EV1, Kolyubaeva SN1, Kutelev GG1, Tyrenko VV1
-
Affiliations:
- Military Medical Academy named after S.M. Kirov
- Issue: Vol 102, No 6 (2021)
- Pages: 805-814
- Section: Theoretical and clinical medicine
- URL: https://bakhtiniada.ru/kazanmedj/article/view/63940
- DOI: https://doi.org/10.17816/KMJ2021-805
- ID: 63940
Cite item
Abstract
Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes.
Methods. The study included 436 young people (mean age 19.8±1.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric Kruskal–Wallis test, the Mann–Whitney U-test, the Pearson’s chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used.
Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 G>A in the LIPC gene had the highest sensitivity, specificity, and accuracy.
Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.
Full Text
##article.viewOnOriginalSite##About the authors
V A Kachnov
Military Medical Academy named after S.M. Kirov
Author for correspondence.
Email: kvasa@mail.ru
Russian Federation, Saint-Petersburg, Russia
E V Kryukov
Military Medical Academy named after S.M. Kirov
Email: kvasa@mail.ru
Russian Federation, Saint-Petersburg, Russia
S N Kolyubaeva
Military Medical Academy named after S.M. Kirov
Email: kvasa@mail.ru
Russian Federation, Saint-Petersburg, Russia
G G Kutelev
Military Medical Academy named after S.M. Kirov
Email: kvasa@mail.ru
Russian Federation, Saint-Petersburg, Russia
V V Tyrenko
Military Medical Academy named after S.M. Kirov
Email: kvasa@mail.ru
Russian Federation, Saint-Petersburg, Russia
References
- Malkov P.V., Baranov E.F., Bezborodova T.S., Bobylev S.N., Bugakova N.S., Vagan I.S., Gokhberg L.M., Grigor'ev L.M., Egorenko S.N., Elizarov V.V., Ivanov Yu.N., Kevesh A.L., Kenchadze D.D., Klochkova E.N., Kosarev A.E., Laykam K.E., Maleva T.M., Nesterov V.N., Okladnikov S.M., Oksenoyt G.K., Ryabushkin B.T., Smelov P.A., Surinov A.E., Tatarinov A.A., Khamzin R.A., Khoroshilov A.V., Shapoval I.N. Rossiyskiy statisticheskiy ezhegodnik. (Russian statistical yearbook.) 2019. M.: Rosstat. 2019; 708 р. (In Russ.)
- Shlyakhto E.V., Arutyunov G.P., Belenkov Yu.N., Bojcov S.A. Natsio¬nal’nye rekomendatsii po opredeleniyu riska i profilaktike vnezapnoy serdechnoy smerti. (National guidelines for risk assessment and prevention of sudden cardiac death.) 2nd ed. Moscow: Medpraktika-M. 2018; 247 p. (In Russ.)
- Linchak R.M., Nedbaykin A.M., Sementsova E.V., Yusova I.A, Strukova V.V. Incidence and structure of sudden cardiac death among working population of the Bryansk region. GERMINA re-gister data. Rational pharmacotherapy in cardiology. 2016; 12 (1): 45–50. (In Russ.) doi: 10.20996/1819-6446-2016-12-1-45-50.
- Boytsov S.A., Nikulina N.N., Yakushin S.S., Akinina S.A., Furmenko G.I. Sudden cardiac death in patients with coronary heart disease: results of the Russian multi-centre epidemiological study of mortality, morbidity, and diagnostics and treatment quality in acute CHD (resonance). Russian Journal of Cardiology. 2011; 16 (2): 59–64. (In Russ.)
- Zaitsev D.N., Vasilenko P.V., Govorin A.V., Vasilenko E.A., Mukha N.V., Filev A.P., Brizhko A.N., Petrova N.G., Sazonova E.A. 2017–2019 Sudden cardiac death registry of the Zabaykalsky Krai population (ZODIAC). Russian Journal of Cardiology. 2020; 25 (11): 108–114. (In Russ.) doi: 10.15829/1560-4071-2020-3997.
- Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., Chapman M.J., De Backer G.G., Delgado V., Ference B.A., Graham I.M., Halliday A., Landmesser U., Mihaylova B., Pedersen T.R., Riccardi G., Richter D.J., Sabatine M.S., Taskinen M., Tokgozoglu L., Wiklund O. 2019 ESC/EAS Guidelines for themanagement of dyslipidaemias: lipid modification to reduce cardiovascular risk. Russian Journal of Cardiology. 2020; 25 (5): 121–193. (In Russ.) doi: 10.15829/1560-4071-2020-3826.
- Abondio P., Sazzini M., Garagnani P., Boattini A., Monti D., Franceschi C., Luiselli D., Giuliani C. The gene¬tic variability of APOE in different human populations and its implications for longevity. Genes. 2019; 10: 222. DOI: 10. 3390/genes10030222.
- Farup P.G., Rootwelt H., Hestad K. APOE — a genetic marker of comorbidity in subjects with morbid obesity. BMC Med. Genet. 2020; 21 (1): 146. doi: 10.1186/s12881-020-01082-2.
- Norata G.D., Tsimikas S., Pirillo A., Catapano A.L. Apolipoprotein C-III: From pathophysiology to pharmacology. Trends Pharmacol. Sci. 2015; 36: 675–687. doi: 10.1016/j.tips.2015.07.001.
- Wei L.K., Au A., Teh L.K., Lye H.S. Recent advan¬ces in the genetics of hypertension. Adv. Exp. Med. Biol. 2017; 956: 561–581. doi: 10.1007/5584_2016_75.
- Lin B., Huang Y., Zhang M., Wang J., Wu Y. Association between apolipoprotein C3 Sst I, T-455C, C-482T and C1100T polymorphisms and risk of coronary heart di¬sease. BMJ Open. 2014; 4 (1): e004156. doi: 10.1136/bmjopen-2013-004156.
- Rodriguez Esparragon F., Lopez Fernandez J.C., Buset Rios N., García-Bello M.A., Hernández-Velazquez E., Cappiello L., Rodríguez-Pérez J.C. Paraoxonase 1 and 2 gene variants and the ischemic stroke risk in Gran Canaria population: An association study and meta-analysis. Int. J. Neurosci. 2017; 127 (3): 191–198. doi: 10.3109/00207454.2016.1165675.
- Elkina A.Yu., Akimova N.S., Schwartz Yu.G., Martynovich T.V., Fedotov E.A. Vascular control parameters and gene polymorphism associated with cardiovascular risk in young and relatively healthy indivi¬duals. Kardiovaskulyarnaya terapiya i profilaktika. 2019; 18 (2): 45–50. (In Russ.) doi: 10.15829/1728-8800-2019-2-45-50.
- Zhang Z., Ou J., Cai P., Niu B., Li J. Association between the PON1 Q192R polymorphism and coronary heart disease in Chinese: a meta-analysis. Medicine (Baltimore). 2018; 97 (26): e11151. doi: 10.1097/MD.0000000000011151.
- Wang J., Du S., Wang J., Zhu M., Wen X., Yang W. Association of the lipoprotein lipase gene Ser447Ter polymorphism with hypertension and blood pressure variation: Evidence from an updated meta-analysis. Clin. Exp. Hypertens. 2017; 39 (7): 655–664. doi: 10.1080/10641963.2017.1313848.
- Zhao X., Ren Y., Li H., Wu Y. Association of LIPC –250G/A and –514C/T polymorphisms and hypertension: A systematic review and meta-analysis. Lipids Health Dis. 2018; 17 (1): 238. doi: 10.1186/s12944-018-0884-4.
- Verma P., Verma D.K., Sethi R., Singh S., Krishna A. The rs2070895 (-250G/A) single nucleotide polymorphism in hepatic lipase (HL) gene and the risk of coronary artery disease in North Indian population: a case-control study. J. Clin. Diagn. Res. 2016; 10 (8): GC01–GC06. doi: 10.7860/JCDR/2016/20496.8378.
- Kulminski A.M., Raghavachari N., Arbeev K.G., Culminskaya I., Arbeeva L., Wu D., Ukraintseva S.V., Christensen K., Yashin A.I. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the long life family study. Biogerontology. 2016; 17: 893–905. doi: 10.1007/s10522-016-9659-3.
- Au A., Griffiths L.R., Irene L., Kooi C.W., Wei L.K. The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis. Atherosclerosis. 2017; 265: 60–70. doi: 10.1016/j.atherosclerosis.2017.08.003.
- Trishkin D.V., Fisun A.Ya., Makiev R.G., Cherkashin D.V. Current state and prospects of development of personalized medicine, high-tech health care and health saving technologies in the medical service of the Armed forces of the Russian Federation. Bulletin of the Russian Military medical academy. 2019; (3): 145–150. (In Russ.)
- Cao L., Li Q., Chen X. The HindIII and PvuII polymorphisms of lipoprotein lipase (LPL) gene reduce the risk of ischemic stroke (IS): a meta-analysis. Medi¬cine (Baltimore). 2018; 97 (18): e0483. doi: 10.1097/MD.0000000000010483.
- Ren L., Ren X. Meta-analyses of four polymorphisms of lipoprotein lipase associated with the risk of Alzheimer's disease. Neurosci. Lett. 2016; 619: 73–78. doi: 10.1016/j.neulet.2016.03.021.
- Goodarzynejad H., Boroumand M., Behmanesh M., Ziaee S., Jalali A., Pourgholi L. Association between the hepatic lipase promoter region polymorphism (−514 C/T) and the presence and severity of premature coronary artery disease. J. Tehran. Heart Cent. 2017; 12: 119–127. PMID: 29062379.
Supplementary files
