GENETIC ASPECTS OF ATRIAL FIBRILLATION ON THE BACKGROUND OF ARTERIAL HYPERTENSION IN COMBINATION WITH NONCARDIAC DISEASES
1Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University, Novosibirsk, Russian Federation
2Research Institute of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation
Objective: To study genetic determinants in patients with atrial fibrillation (AF) on the background of arterial hypertension (AH) in combination with various extracardiac comorbid pathology.
Methods: In a prospective cohort study included 167 patients with paroxysmal and persistent forms of AF and stage II hypertension without CAD. The average age of the patients studied was 53.3±7.1 years. DNA isolation from blood leukocytes was carried out by phenol-chloroform extraction. Testing polymorphism rs2200733, polymorphism 174G/C (174G/C (rs1800795) gene IL6), the IL6 gene performed with PCR with RFLP. Testing of statistical hypotheses was carried out at a critical level of significance p=0.05, i.e. the difference was considered statistically significant at p<0.05. The lower limit of the evidential power was taken equal to 80%.
Results: This study shows associations of polymorphisms 174G/C (rs1800795) of the IL6 gene, the IL6 gene and rs2200733 chromosome 4q25 with AF on the background of comorbidities: AH, chronic obstructive pulmonary disease, hypothyroidism, T2DM, abdominal obesity. Associations of polymorphism 174G/C (rs1800795) of the IL6 gene with the risk of recurrence of AF on the background of individual comorbidities were also found; polymorphism rs2200733 chromosome 4q25 with triglyceride levels, index atherogenicity, creatinine, fibrinogen, with the number of months before the development of relapse; 174G/C (rs1800795) of the IL6 gene – with HDL cholesterol levels, creatinine, diastolic blood pressure, galectin-3.
Conclusions: The results contributes to the study of such a complex phenomenon as the secondary form of atrial fibrillation, contributes to the accumulation of knowledge, bringing closer the time when therapeutic interventions will be individualized, based on an understanding of the pathological process in each patien
Keywords: Atrial fibrillation, polymorphism, rs2200733, 174G/C (rs1800795) of the IL6 gene, IL6, extracardiac pathology.
- Shlyakhto EV, Ezhov AV, Zenin SA. Klinicheskiy portret patsienta s fibrillyatsiey predserdiy v Rossiyskoy Federatsii. Global’nyy registr dannykh GLORIAAF [Clinical portrait of a patient with atrial fibrillation in the Russian Federation. Global register data GLORIAAF]. Kardiologicheskiy zhurnal. 2017;9:21-7.
- Martsevich SYu, Navasardyan AR, Kutishenko NP. Opyt izucheniya mertsatel’noy aritmii na osnove registrovogo profilya [Experience in studying atrial fibrillation on the basis of a register profile]. Ratsional’naya farmakoterapiya. 2017;6:78-92.
- Podzolkov V, Tarzimanova A, Pisarev M, Gataulin R, Mokhammadi L. Statiny v vtorichnoy profilaktike mertsatel’noy aritmii u bol’nykh gipertonicheskoy bolezn’yu. 27 Evropeyskoe soveshchanie po gipertonii i zashchite serdechno-sosudistoy sistemy [Statins in secondary prevention of atrial fibrillation in hypertensive patients. 27th European meeting on hypertention and cardiovascular protection]. 2017;35(2):205. Available from: http://dx.doi.org/10.1592.phco.31.11.1051.
- Leonova EI, Shekhyan GG, Zadionchenko VS. Prediktory mertsatel’noy aritmii u bol’nykh khronicheskoy obstruktivnoy bolezn’yu lyogkikh [Predictors of atrial fibrillation in patients with chronic obstructive pulmonary disease]. Klinicheskaya meditsina. 2016;34(8):1655-8. Available from: http://dx.doi.org/10.1097/hjh.0000000000000983.
- Unger RH, Scherer PE. Gluttony, sloth and metabolic syndrome: a roadmap to lipotoxisity. Trends Endocrinol Metab. 2010;21(6):345-52. Available from: http://dx.doi.org/10.1016/j.tem.2010.01.009.
- Volchkova EA, Nikitin AG, Zotova IV, Zateyshchikova AA, Shavrin IV, Safaryan VI, i dr. Assotsiatsiya mertsatel’noy aritmii u patsientov s khronicheskoy obstruktivnoy bolezn’yu lyogkikh s polimorfizmom gema interleykina-6 [Association of atrial fibrillation in patients with chronic obstructive pulmonary disease with interleukin-6 gene polymorphism]. Kardiologiya. 2015;11:31-6. Available from: http://dx.doi.org/10.18565/ cardio.2015.11.31.31-36.
- Titov BV, Barsova RM, Martynov MYu, Nikonova AA, Favorov AV, Gusev EI, i dr. Polimorfnye varianty genov, kodiruyushchihk interleykin-6 i fibrinogen, risk razvitiya ishemicheskogo insul’ta i urovnya fibrinogena [Polymorphic variants of genes encoding interleukin-6 and fibrinogen, the risk of ischemic stroke and fibrinogen levels]. Molekulyarnaya biochimiya. 2012;46:93-102.
- Newton-Cheh C, Johnson T, Gateva V, Tobin, MD, Bochud, M. Genomewide association study identifies eight loci associated with blood pressure. Nat Genet. 2009;41(6):666-76. Available from: http://dx.doi.org/10.1038/ ng.361.
- Hong KW, Go MJ, Jin HS, Lim JE, Lee JY, Han BG, et al. Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts. J Hum Hypertens. 2010;24(6):367-72.
- Ding K, Kullo IJ. Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease. BMC Med Genet. 2011;20:12-55. Available from: http://dx.doi.org/10.1186/1471-2350-12-55.
- Jeemon P, Pettigrew K, Sainsbury C, Prabhakaran D, Padmanabhan S. Implications of discoveries from genome-wide association studies in current cardiovascular practice. World J Cardiol. 2011;3(7):230-47.
- Xi B, Shen Y, Reilly KH, Wang X, Mi J. Recapitulation of four hypertension susceptibility genes in East Asians. Metabolism. 2013;62(2):196-203
- Xi B, Zhao X, Chandak GR, Shen Y, Cheng H, Hou D, et al. Influence of obesity on association between genetic variants identified by genomewide association studies and hypertension risk in Chinese children. Am J Hypertens. 2013;26(8):990-6.
- AlSaleh A, Maniou Z, Lewis FJ, Hall WL, Sanders TA, O’Dell SD; MARINA Study Team. Interaction between a CSK gene variant and fish oil intake influences blood pressure in healthy adults. J Nutr. 2014;144(3):267-72.
- Gretarsdottir S, Thorleifsson G, Manolescu A, Styrkarsdottir U, Helgadottir A, Gschwendtner A, et al. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann Neurol. 2008;64(4):402-9.
- Kааb S, Darbar D, van Noord Cet. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J. 2009;30(7):813-9.
- Goodloe AH, Herron KJ, Olson TM. Uncovering at intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation. Am J Cardiol. 2011;107(12):182-5.
- Henningsen KM, Olesen MS, Haunsoe S, Svendsen JH. Association of rs2200733 at 4q25 with early onset of lone atrial fibrillation in young patients. Scand Cardiovasc J. 2011;45(6):324-6.
- Parvez B, Shoemaker MB, Muhammad R, Jiang, L, Blair MA. Common genetic polymorphism at 4q25 locus predicts atrial fibrillation recurrence after successful cardioversion. Heart Rhythm. 2013;10(6):849-55.
- Shoemaker MB, Muhammad R, Parvez B, Richardson R, Jiang L, Blair MA. Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation. Heart Rhythm. 2013;10(3):394- 400.
- Olesen MS, Holst AG, Jabbari J, Nielsen JB, Christophersen IE, Sajadieh A. Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years. Can J Cardiol. 2012;28(2):191-5.
- Ritchie MD, Rowan S, Kucera G, Stubblefield T, Blair M, Carter S, 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.
- Lahtinen AM, Noseworthy PA, Havulinna AS, Jula A, Karhunen PJ. Common genetic variants associated with sudden cardiac death: the FinSCDgen study. PLoS ONE. 2012;7(7):416-75.
- Mohanty S, Santangeli P, Bai R, Di Biase L, Mohanty P, Pump A, et al. Variant rs2200733 on chromosome 4q25 confers increased risk of atrial fibrillation: evidence from a meta-analysis. J Cardiovasc Electrophysiol. 2013;24(2):155-61
- Kolek MJ, Parvez B, Muhammad R, Shoemaker MB, Blair MA, Stubblefield T. A common variant on chromosome 4q25 is associated with prolonged PR interval in subjects with and without atrial fibrillation. Am J Cardiol. 2014;113(2):309-13.
- Wasmer K, Unrath M, Köbe J, Malyar NM, Freisinger E. Atrial fibrillation is a risk marker for worse in-hospital and long-term outcome in patients with peripheral artery disease. Int J Cardiol. 2015;111(1):199-221.
- Body SC, Collard CD, Shernan SK, Fox AA, Liu KY, Ritchie MD, et al. Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery. Circ Cardiovasc Genet. 2009;2(5):499-506.
- Virani SS, Brautbar A, Lee VV, MacArthur E, Morrison AC, Grove ML, et al. Usefulness of single nucleotide polymorphism in chromosome 4q25 to predict in-hospital and long-term development of atrial fibrillation and survival in patients undergoing coronary artery bypass grafting. Am J Cardiol. 2011;107(10):1504-9.
Khidirova Lyudmila Daudovna , Candidate of Medical Sciences, Associate Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University ORCID ID: 0000-0002-1250-8798
Yakhontov Davyd Aleksandrovich ,Doctor of Medical Sciences, Professor of the Department of Pharmacology, Clinical Pharmacology and EvidenceBased Medicine, Novosibirsk State Medical University ORCID ID: 0000-0003-4735-5178
Maksimov Vladimir Nikolaevich , Doctor of Medical Sciences, Full Professor, Head of the Laboratory of Molecular Genetic Research of Therapeutic Diseases, Research Institute of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Address for correspondence:
Khidirova Lyudmila Daudovna
Candidate of Medical Sciences, Associate Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine, Novosibirsk State Medical University
630091, Russian Federation, Novosibirsk, Red Avenue, 52
Tel.: +7 (923) 1129218
Materials on the topic:
- APPLICATION OF A TWO-STEP SCREENING SYSTEM IN COMPLEX EVALUATION OF PSYCHOSOCIAL STATUS IN PATIENTS WITH CORONARY HEART DISEASE
- FEATURES OF REMODELLING OF THE LEFT VENTRICULAR MYOCARDIUM IN PATIENTS WITH ARTERIAL HYPERTENSION OF ELDERLY AGE WITH COMORBID DEPRESSION
- TREATMENT OF CHRONIC HEART FAILURE IN MIDDLE-AGED MEN WITH DEPRESSION
- GENDER STEREOTYPES OF THE PERSONALITY AND FAMILY SETTINGS IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
- THE INFLUENCE OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON SPECTRAL INDICES OF HEART RHYTHM IN PATIENTS WITH HIV INFECTION
- HIGH-TECHNOLOGICAL MEDICAL AID IN ACUTE CORONARY SYNDROME IN THE UDMURT REPUBLIC
- INFLUENCE OF THE MAIN LEFT CORONARY ARTERY DISEASE ON THE LEFT VENTRICULAR CONTRACTILE FUNCTION IN THE LONG TERM PERIOD