EFFECT OF POLYMORPHISM OF APOE AND SLCO1B1 GENES ON THE COURSE OF MYOCARDIAL INFARCTION ASSOCIATED WITH ACUTE KIDNEY INJURY IN HOSPITAL AND LONG-TERM PERIODS

THE AIM: to assess the effect of APOE and SLCO1B1 gene polymorphism on the course of myocardial infarction (MI) associated with acute kidney injury (AKI) in hospital and long-term periods.

PATIENTS AND METHODS: 132 patients with МI were examined, which were divided into 2 groups: the first (I) – 68 patients with MI and AKI, the second (II) – 64 people with MI without AKI.

RESULTS: In the distribution of genotypes, polymorphism of Leu28Pro of the APOE gene in the studied groups was revealed that LeuPro was more often inherited in patients of group I – 20,6 %, the average value of total cholesterol (TC) – 6,01±0,3 mmol/l, and low density lipoproteins (LDL) – 3,37±0,21 mmol/l, compared with patients of group II, where the LeuPro genotype – 6, 2 %, TC – 5,03±0,3 mmol/l, LDL – 2,38±0,3 mmol/l, p<0,05. A similar situation was typical for the polymor phism Val174Ala SLCO1B1 gene, where ValAla in patients of group I-26,5 %, in II-12,5 %, p<0.05. In heterozygotes I sample TC-5,59±0,3 mmol/l, and LDL – 3,30±0,14 mmol/l, in group II TC – 5,19±0,29 mmol/l, LDL – 2,75±0,23 mmol / l, p<0,05. The clinical picture of the hospital period in patients with MI and AKI, proceeded with the development of a greater number of complications, which reflected in the high mortality in group I – 16,2 %, in group II – 4,7 %, p<0,05. In the posthospital period, against the background of atorvastatin administration in both study groups, there was a positive trend of decrease in TC and LDL, but it was not possible to achieve the targets. Mortality in the long-term period in group I – 15,4 %, in group II-2,0 %, p<0.05.

CONCLUSIONS: in patients with MI and AKI on the background of a more severe clinical course of the disease, both in hospital and in the long-term period, rare allelic variants of the genes APOE and SLCO1B1 were more often determined, which negatively affected the lipid profile.

1. Rossijskoe kardiologicheskoe obshchestvo. Nacionalnoe obshchestvo po izucheniyu ateroskleroza. Rossijskoe obshchestvo kardiosomaticheskij reabilitacii i vtorichnoj profilaktiki. Diagnostika i korrekciya narushenij lipidnogo obmena s celyu profilaktiki i lecheniya ateroskleroza. Rossijskie rekomendacii (v peresmotr). Rossijskij kardiologicheskij zhurnal 2012; (4): 4–32. doi:org/10.15829/1560-4071-2012-4s1.

2. Rossijskoe kardiologicheskoe obshchestvo. Nacionalnoe obshchestvo po izucheniyu ateroskleroza. Rossijskoe obshchestvo kardiosomaticheskij reabilitacii i vtorichnoj profilaktiki. Diagnostika i korrekciya narushenij lipidnogo obmena s cel'yu profilaktiki i lecheniya ateroskleroza. Rossijskie rekomendacii (V I peresmotr). Ateroskleroz i Dislipidemii 2017; 28(3):5–23

3. Sychev DA, Semenov AV, Ramenskaya GV et al. Pharmacogenetics of HMG-CoA reductase inhibitors (statins): perspectives of individualized, genotype-based therapy. Сardiovascular therapy and prevention 2006;5(1):100–104. doi: 10.1016/j.atherosclerosis.2004.09.004

4. Heng CK, Saha N, Tay JS. Lack of association of apolipoprotein E polymorphism with plasma Lp(a) levels in the Chinese. Clin.Genetics 1995; (48): 120–153. PMID:8556815

5. Shuev GN, Sychev DA, Grachev AV. Gene polymorphism of SLCO1B1, associated with the development of statin-induced myopathy, levels of vitamin D in Russian patients with hyperlipidemia. Сreative cardiology 2015; (4):40–45. doi: 10.15275/kreatkard.2015.04.05

6. Petrov VI, Smuseva ON, Solovkina YV et al. The SLCO1B1 gene polymorphism and statin-induced myopathy in russian patients. Russian Journal of Cardiology 2014;(10):69–72. doi.org/10.15829/1560-4071-2014-10-69-072

7. Khokhlov AA, Sychev DA. Safety of statins in terms of evidence of evidence medicine: pharmacogenetic, pharmacokinetic aspects. Health standardization problems 2015; (7-8): 21–27

8. KDIGO Clinical Practice Guideline for Acute Kidney Injury Kidney International supplements. Kidney International supplements Volume 2/issue 1/ March 2012 http://www.kidneyinternational.org.

9. Smirnov AV, Dobronravov VA, Rumyantsev ASh, Kayukov IG. Acute kidney injury. Medical information Agency, M., 2015; 228–238

10. Smirnov АV, Kayukov IG, Dobronravov VA, Kucher AG. Acute kidney injury – a new definition in nephrology. Clinical nephrology 2009; 1: 11–15

11. Utennan G, Steinmetz A, Weber W. Genetic control of human apolipoprotein E polymorphism: comparison of оne- and two- dimensional techniques of isoprotein, analysis. Hum Genet 1982; (60): 344–351. doi https://doi.org/10.1007/BF00569216

12. Siverina AV, Skorodumova EA, Kostenko VA et al. Genetic variants of functioning of the key pathogenetic mechanisms in patients with myocardial infarction and acute cardiorenal syndrome. Translational medicine 2017; 4(6): 6–12. https://doi.org/10.18705/2311-4495-2017-4-6-6-12

13. Marenzi G, Gabiati A, Bertoli SV, et al. Incidence and relevance of acute kidney injury in patients hospitalized with acute coronary syndromes. Am J Cardiol 2013; 20 (1): 816–822

14. Arutiunov GP, Oganezova LG. Acute myocardial infarction and kidney function. Clinical nephrology 2010; 3: 39–43