GENETIC PREDICTORS FOR CARDIOEMBOLIC STROKE IN PATIENTS WITH ATRIAL FIBRILLATION

Aim. To reveal genetic predictors of the ischemic stroke in patients with AF.
Material and methods. Totally 121 patient studied with AF and 155 their relatives of I-III grade of relation. First group consisted of 43 probands with AF and stroke anamesis and 54 their relatives, the second group – 78 probands with AF without stroke and 101 their relative. Control group consists of 188 subjects. The patients underwent ECG, EchoCG, Holter ECG-monitoring, VEM, TELAS, molecular-genetic investigation.
Results. Genotype AA of polymorphism -455 G>A of gene FGB statistically significantly predominated in subjects with AF and stroke comparing to those with AF without stroke (20,94% vs 6,4%; p=0,036). Risk relation shows that the chance of stroke development with AA homozygous genotype at rare allele is 3,9 times higher than in its absence. Overall the genotypes CT and TT by the rare allele 807C>T gene ITGA2 statistically significantly predominated in the patients with AF and stroke comparing to controls (76,7% vs 56,9%, p=0,026). The chance of stroke development while carrying CT and TT by the rare allele is 2,5 times higher than in their absence. Genotypes TC and CC by the rare polymorphism 5 T>C gene GPIBA statistically more significantly were found in patients with AF and credibly increases
the chance for stroke 2,3 times. Allele A of polymorphism 10796 G>A gene F7 statistically more significant rarer found in patients with AF and stroke comparing to controls (6,98% vs 16,22%; p=0,043). Chance of stroke in absence of allele A is 2,6 times higher, than in its presence.
Conclusion. The study revealed that homozygous genotype AA by the rare polymorphism -455G>A gene FBG, heterozygous CT and homozygous TT by the rare allele 807C>T gene ITGA2, heterozygous TC anf homozygous CC by the rare – 5 T>C gene GPIAB are set as genetic predictors for ischemic stroke development in AF. Allele A of the polymorphism 10976 G>A gene F7 show protective effect in the ischemic stroke development in AF. Genetic risk estimation might improve the primary ischemic stroke prevention in AF.

1. Diagnostics and treatment of fibrillation of auricles. RCS, ARSA and ACVS recommendations. Russ J Cardiol. 2013; 4: App. 3. Russian (Диагностика и лечение фибрилляции предсердий. Рекомендации РКО, ВНОА и АССХ. Российский кардиологический журнал 2013, 4: приложение 3).

2. Zotova I, Brovkin A, Isaeva M, et al. Factor V polymorphism associated with left atrial thrombosis in patients with nonvalvular atrial fibrillation. Atherosclerosis thrombosis and vascular biology annual conference. Atlanta 2008: 125.

3. Berge E, Haug K, Sandset EC, et al. The factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT and platelet glycoprotein IIIa 1565TC mutations in patients with acute ischemic stroke and atrial fibrillation. Stroke 2007; 38: 1069—71.

4. Roldan V, Marin F, Gonzalez-Conejero R, et al. Factor VII-323 decanucleotide D/I polymorphism in atrial fibrillation: Implications for the prothrombotic state and stroke risk. Ann. Med. 2008, 40: Iss. 7: 553—9.

5. Bozdemir V, Kirimli O, Akdeniz B, et al. Beta-fibrinogen 455 G/A gene polymorphism is associated with the left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation. Anadolu Kardiyol. Derg. 2010, 10: 209—15.

6. Zateyshchikov DA, Brovkin AN, Chistiakov DA, et al. Advanced age, low left atrial appendage velocity, and Factor V promoter sequence variation as predictors of left atrial thrombosis in patients with nonvalvular atrial fibrillation. J. Thromb. Thrombolysis 2010, 30: Iss. 2: 192—9.

7. Ritchie MD, Rowan S, Kucera G, et al. Chromosome 4q25 variants are genetic modifiers of rare ion channel mutations associated with familial atrial fibrillation. J. Am. Coll. Cardiol. 2012, 60; 13: 1173—81.

8. Nikulina SYu, Shulman VA, Aksyutina NV, et al. Idiopathic fibrillation of auricles. Ross. cardiology: from the center to regions, congress materials. Tomsk 2004; 353. Russian (Никулина С.Ю., Шульман В.А., Аксютина Н.В. и др. Идиопатическая фибрилляция предсердий. Росс. кардиология: от центра к регионам, материалы конгресса. Томск.: 2004; 353).

9. Illarioshkin SN. Genetics of vascular diseases of the brain. Essay angioneurology. Edited by Z.A. Suslina. M.: Atmosphere; 2005. Russian (Иллариошкин, С.Н. Генетика сосудистых заболеваний мозга. Очерк ангионеврологии. Под ред. З.А. Суслиной. М.: Атмосфера; 2005).

10. Bozdemir V, Kirimli O, Akdeniz B, et al. Beta-fibrinogen 455 G/A gene polymorphism is associated with the left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation. Anadolu Kardiyol. Derg. 2010; 10: 209—15.

11. Kritzik M, Savage B, Nugent DJ, et al. Nucleotide polymorphisms in the alpha 2 gene define multiple alleles which are associated with differences in platelet alpha 2 beta 1. Blood. 1998; 92: 2382-8.

12. Voronina EN, Filipenko ML, Sergeevichev DS, et al. Membrane receptors platelets: functions and polymorphism. Messenger VMGS. 2006, Volume 10, 3: 553-64. Russian (Воронина Е. Н., Филипенко М. Л., Сергеевичев Д. С. и др. Мембранные рецеп- торы тромбоцитов: функции и полиморфизм. Вестник ВОГиС. 2006, Том 10, 3: 553-64).

13. Staikov DA, Zotova IV, Dankowtsewa EN, et al. Thrombosis and antithrombotic therapy in adults. Moscow, 2011. Russian (Затейщиков Д. А., Зотова И. В., Данковцева Е. Н. и др. Тромбозы и антитромботическая терапия при аритмиях. Москва, 2011).