Association of polymorphic variants of a number of candidate genes for lipid and carbohydrate metabolism with the risk of myocardial infarction: results of a single-center, cross-sectional study

Aim of the study was to determine the association of polymorphic variants of lipid and carbohydrate metabolism genes with the risk of myocardial infarction.

Material and methods. 146 patients with myocardial infarction and 300 relatively healthy donors were recruited for the molecular genetic study including isolation of genomic DNA and genotyping of single-nucleotide polymorphic variants by real-time PCR. To assess the myocardial infarction risk, the frequencies of alleles and genotypes for 12 single-nucleotide polymorphic variants in the IGF1R, INS, LEP, LEPR, LIPC, LPA, APOE and APOB genes were studied.

Results. It was found that the increased myocardial infarction risk is associated with the genotypes T/T and G/T of rs6725189 variant in the APOB gene (p < 0.0001); G/G and A/G of rs1137100 variant in the LEPR gene (p < 0.0001) and T/T of rs1800588 variant in the LIPC gene (p = 0.0023) regardless of gender. In men, the myocardial infarction risk is 1.5-fold higher than in women when carrying a homozygous genotype for a rare allele of the polymorphic loci rs1800588 in the LIPC gene (p = 0.0064) and rs6725189 in the APOB gene (p < 0.0001). Carriage of the A allele of rs689 variant in the INS gene (p = 0.024) and the C allele of rs429358 variant in the APOE gene (p = 0.024) increases the myocardial infarction risk in men by two times. At the same time, the A/G and G/G genotypes of the rs1137101 polymorphic variant in the LEPR gene are associated with a reduced myocardial infarction risk (p = 0.0003). Myocardial infarction patients carrying the C/C genotype of rs7412 variant in the APOE gene are characterized by higher serum blood level of LDL (p = 0.0091), and this tendency is more pronounced in men (p = 0.044). In male patients with myocardial infarction carrying the homozygous for the rare allele A of the polymorphic variant rs689 in the INS gene, higher fasting glucose levels were recorded (p = 0.01).

Conclusions. Carriage of rare alleles in individual polymorphic sites of the genes of lipid (rs1137100 LEPR, rs6725189 APOB, rs1800588 LIPC and rs429358 APOE) and carbohydrate metabolism (rs689 INS) is associated with an increased risk of myocardial infarction.

1. Sedykh D.Yu., German A.I., Khryachkova O.N., Kashtalap V.V., Barbarash O.L. Three year prognosis of patients with myocardial infarction depending on the body weight index: data of the Kemerovo acute coronary syndrome registry. Ratsional’naya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology. 2022;18(1):4–11 [In Russian]. doi: 10.20996/1819-6446-2022-02-08

2. Zuin M., Rigatelli G., Temporelli P., di Fusco S.A., Colivicchi F., Pasquetto G., Bilato C. Trends in acute myocardial infarction mortality in the European Union, 2012–2020. Eur. J. Prev. Cardiol. 2023;30(16):1758–1771. doi: 10.1093/eurjpc/zwad214

3. Wang Y., Xian H. Identifying genes related to acute myocardial infarction based on network control capability. Genes (Basel). 2022;13(7):1238. doi: 10.3390/genes13071238

4. Khryachkova O.N., Khutornaya M.V., Sinitskaya A.V., Sinitskiy M.Yu., Kashtalap V.V. Polymorphic variants of LEP and LEPR genes in patients with myocardial infarction: association with serum leptin and its soluble receptor levels. Russkiy meditsinskiy zhurnal. Meditsinskoye obozreniye = Russian Medical Journal. Medical Review. 2024;8(1):4–8 [In Russian]. doi: 10.32364/2587-6821-2024-8-1-1

5. Khutornaya M.V., Khryachkova O.N., Sinitskaya A.V., Poddubnyak A.O., Ponasenko A.V., Kashtalap V.V. Role of the genes of the natriuretic peptide and antioxidant defense systems in creating the risk of myocardial infarction development (the preliminary results of a pilot study). Russkiy meditsinskiy zhurnal. Meditsinskoye obozreniye = Russian Medical Journal. Medical Review. 2023;7(1):5–12 [In Russian]. doi: 10.32364/2587-6821-2023-7-1-5-12

6. Kozik V.A., Shpagina L.A., Shpagin I.S., Minnikh S.V., Lozhkina N.G., Maksimov V.N. Search for genetic predictors of acute coronary syndrome in patients after coronavirus disease 2019. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2024;29(10):7–12 [In Russian]. doi: 10.15829/1560-4071-2024-5953

7. Kozik V.A., Shpagina L.A., Shpagin I.S., Maksimova S.V., Lozhkina N.G., Maksimov V.N. Assessment of the association of the rs12329760 polymorphism of the TMPRSS2 gene with acute cor onary syndrome in patients with new coronavirus infection. Ateroskleroz = Ateroscleroz. 2024;20(1):35–41 [In Russian]. doi: 10.52727/2078-256X-2024-20-1-35-41

8. Taha M., Ibrahim M.M.M., Sedrak H. Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients. Gene. 2024;895:147976. doi: 10.1016/j.gene.2023.147976

9. Abd El-Aziz T.A., Mohamed R.H. LDLR, ApoB and ApoE genes polymorphisms and classical risk factors in premature coronary artery disease. Gene. 2016;590(2):263–269. doi: 10.1016/j.gene.2016.05.032

10. Roszkowska-Gancarz M., Kurylowicz A., Polosak J., Mossakowska M., Franek E., Puzianowska-Kuźnicka M. Functional polymorphisms of the leptin and leptin receptor genes are associated with longevity and with the risk of myocardial infarction and of type 2 diabetes mellitus. Endokrynol. Pol. 2014;65(1):11–16. doi: 10.5603/EP.2014.0002

11. Baroni M.G., Berni A., Romeo S., Arca M., Tesorio T., Sorropago G., Di Mario U., Galton D.J. Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD. BMC Med. Genet. 2003;4:8. doi: 10.1186/1471-2350-4-8

12. Hindorff L.A., Lemaitre R.N., Smith N.L., Bis J.C., Marciante K.D., Rice K.M., Lumley T., Enquobahrie D.A., Li G., Heckbert S.R., Psaty B.M. Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke. Pharmacogenet. Genomics. 2008;18(8):677–682. doi: 10.1097/FPC.0b013e3283033528

13. Ahmad T., Chasman D.I., Buring J.E., Lee I.M., Ridker P.M., Everett B.M. Physical activity modifies the effect of LPL, LIPC, and CETP polymorphisms on HDL-C levels and the risk of myocardial infarction in women of European ancestry. Circ. Cardiovasc. Genet. 2011;4(1):74–80. doi: 10.1161/CIRCGENETICS.110.957290

14. Song X., Zheng Y., Xue W., Li L., Shen Z., Ding X., Zhai Y., Zhao J. Identification of risk genes related to myocardial infarction and the construction of early SVM diagnostic model. Int. J. Cardiol. 2021;328:182–190. doi: 10.1016/j.ijcard.2020.12.007

15. Hryachkova O.N., Sinitskaya A.V., Ponasenko A.V. Cardiovascular risk personification: focus on the natriuretic peptide system. Ateroskleroz = Ateroscleroz. 2023;19(2):131–139 [In Russian]. doi: 10.52727/2078-256X-2023-19-2-131