SLC2A9 Genotype Distribution and Left Atrium Diameter in Patients with Arterial Hypertension and Atrial Fibrillation
- Authors: Snezhitskiy V.A.1, Kopytsky A.V.1, Barysenko T.L.1
-
Affiliations:
- Grodno State Medical University
- Issue: Vol 3, No 1 (2023)
- Pages: 5-15
- Section: Original Research
- URL: https://journals.rcsi.science/cardar/article/view/132564
- DOI: https://doi.org/10.17816/cardar164429
- ID: 132564
Cite item
Abstract
BACKGROUND: In recent years, asymptomatic hyperuricemia (HU) has been found to have significant adverse effects on the cardiovascular system. Uric acid (UA) accumulation in cardiomyocytes may cause ionic and structural remodeling of the atria. One of the causes of increased UA and a significant risk factor for HU is polymorphism in the SLC2A9 gene, which encodes the GLUT9 protein, a highly specific urate transporter in proximal renal tubular cells.
AIM: To investigate the frequency of genotypes and alleles of the SLC2A9 gene rs734553 polymorphism and left atrium (LA) diameter in patients with arterial hypertension (AHT) and atrial fibrillation (AF).
MATERIALS AND METHODS: One hundred four patients, including 94 (90.4%) men and 10 (9.6%) women (aged 55 [45; 61] years old) were enrolled in the study. The patients were divided into the following groups: first — patients with AF (n = 13); second — patients with AHT and AF (n = 68); and third — patients with AHT (n = 23). The LA diameter equal to the LA anterior–posterior dimension on transthoracic echocardiography was taken into account as a characteristic of structural changes of the LA. All patients underwent instrumental, laboratory, and molecular genetic testing, including SLC2A9 gene rs734553 polymorphism using the polymerase chain reaction technique.
The data were presented as median, first and third quartiles, and absolute and relative frequencies. Differences between groups of patients were assessed using the Mann – Whitney U-test and Fisher and Pearson’s χ² test. The Kruskal–Wallis test was used to compare three independent groups. Differences were considered statistically significant at p < 0.05. The relationship between the quantitative and dichotomous variables was described using the rank-biserial correlation coefficient (rrb). The distribution of alleles and genotypes in the studied patient groups was tested for Hardy – Weinberg equilibrium and assessed using the χ2 test.
RESULTS: There were no significant differences (p > 0.05) when comparing the LA diameter and the genotype of the SLC2A9 gene rs734553 polymorphism in all groups of patients. However, in Group 2, the LA diameter in the CC genotype (43 [42; 44] mm) patients and the AC genotype (40 [49; 43] mm) patients was determined to be larger than in the AA genotype ones (38 [38; 42] mm). In Group 1, the LA diameter in the AC genotype patients (40 [38; 42] mm) was larger than in the AA genotype ones (38 [34; 38] mm).
When studying the distribution frequency of genotypes and alleles of the SLC2A9 gene rs734553 polymorphism in patients with LA dilatation, we found that in the second group of patients, the AC genotype was significantly more common than in other groups (23.5%) (p = 0.004), and there was also a trend toward a higher incidence of AA (13.2%) and CC (14.7%) genotypes. However, it did not reach the criteria for statistical significance. It should be noted that in patients of the first group, LA dilatation was diagnosed only with the AC genotype (38.5%). Dilatation of the LA in patients of the third group was not detected.
CONCLUSIONS: In Group 1 patients (with AF), LA dilatation was observed only in the AC genotype ones. In Group 2 patients (with AHT and AF), LA dilatation was significantly more frequent (p = 0.004) in the AC genotype ones. The AC and CC genotype of the SLC2A9 gene rs734553 polymorphism was more frequent in Group 2 patients (with AHT and AF).
Full Text
##article.viewOnOriginalSite##About the authors
Viktor A. Snezhitskiy
Grodno State Medical University
Email: vsnezh@grsmu.by
ORCID iD: 0000-0002-1706-1243
SPIN-code: 1697-0116
MD, PhD, Professor
Belarus, GrodnoAndrei V. Kopytsky
Grodno State Medical University
Email: Andrey_cop@mail.ru
ORCID iD: 0000-0002-1862-4300
SPIN-code: 5247-4972
Senior Lecturer
Belarus, GrodnoTatyana L. Barysenko
Grodno State Medical University
Author for correspondence.
Email: t.kepourko@gmail.com
ORCID iD: 0000-0001-7117-2182
SPIN-code: 9280-0169
AssistantBelarus, Grodno
References
- Molchanova OV, Britov AN, Platonova EV. Importance of elevated uric acid levels in the development and prevention of chronic non-communicable diseases. The Russian Journal of Preventive Medicine. 2020;23(2):102–108. (In Russ.). doi: 10.17116/profmed202023021102
- Volkov VYe. Atrial Fibrillation Associated With Arterial Hypertension. Farmateka. 2011;(14):20–23. (In Russ.).
- Drapkina OM, Kostyukevich MV. Arterial'naya gipertenziya: ot fibrillyatsii predserdii i insul'ta do metabolicheskogo sindroma. Spravochnik poliklinicheskogo vracha. 2010;(8):18–21. (In Russ.).
- Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013;14:164. doi: 10.1186/1471-2369-14-164
- Topolyanskaya SV. Hyperuricemia and cardiovascular diseases. Therapy. 2020;6(7):71–82. (In Russ.). doi: 10.18565/therapy.2020.7.71-82
- Reginato AM, Mount DB, Yang I, Choi HK. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol. 2012;8(10):610–621. doi: 10.1038/nrrheum.2012.144
- Li S, Sanna S, Maschio A, et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet. 2007;3(11):e194. doi: 10.1371/journal.pgen.0030194
- Yi X-L, Li J, Meng D-M, et al. An Intron Variant of SLC2A9 Increases the Risk for Type 2 Diabetes Mellitus Complicated with Hyperuricemia in Chinese Male Population. Iran J Public Health. 2018;47(6):844–851.
- Salas-Burgos A, Iserovich P, Zuniga F, et al. Predicting the three-dimensional structure of the human facilitative glucose transporter glut1 by a novel evolutionary homology strategy: insights on the molecular mechanism of substrate migration, and binding sites for glucose and inhibitory molecules. Biophys J. 2004;87(5):2990–2999. doi: 10.1529/biophysj.104.047886
- Mallamaci F, Testa A, Leonardis D, et al. A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study. Am J Kidney Dis. 2015;65(2):294–302. doi: 10.1053/j.ajkd.2014.07.021
- Gonzalez-Aramburu I, Sanchez-Juan P, Jesus S, et al. Genetic variability related to serum uric acid concentration and risk of Parkinson’s disease. Mov Disord. 2013;28(12):1737–1740. doi: 10.1002/mds.25507
- Testa A, Mallamaci F, Spoto B, et al. Association of a polymorphism in a gene encoding a urate transporter with CKD progression. Clin J Am Soc Nephrol. 2014;9(6):1059–1065. doi: 10.2215/CJN.11041013
- Wallace C, Newhouse SJ, Braund P, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet. 2008;82(1):139–149. doi: 10.1016/j.ajhg.2007.11.001
- Sull JW, Park EJ, Lee M, Jee SH. Effects of SLC2A9 variants on uric acid levels in a Korean population. Rheumatol Int. 2013;33(1): 19–23. doi: 10.1007/s00296-011-2303-2
- Letsas KP, Korantzopoulos P, Filippatos GS, et al. Uric acid elevation in atrial fibrillation. Hellenic J Cardiol. 2010;51(3):209–213.
- Chao T-F, Hung C-L, Chen S-J, et al. The association between hyperuricemia, left atrial size and new-onset atrial fibrillation. Int J Cardiology. 2013;168(4):4027–4032. doi: 10.1016/j.ijcard.2013.06.067
- Liao X, Yu X, Zhou D, Huang Yu. Study on the relationship between left atrial diameter with serum uric acid level in male patients with essential hypertension. Chinese Journal of Primary Medicine and Pharmacy. 2018;(12):1769–1772.
- Hidru TH, Tang Y, Liu F, et al. Does serum uric acid status influence the association between left atrium diameter and atrial fibrillation in hypertension patients? Front Cardiovasc Med. 2020;7:594788. doi: 10.3389/fcvm.2020.594788
- Evropeiskie rekomendatsii po profilaktike serdechno-sosudistykh zabolevanii v klinicheskoi praktike (peresmotr 2012 g.). Russian Journal of Cardiology. 2012;(4s2):4–84. (In Russ.).
- Shalnova SA, Deev AD, Artamonov GV, et al. Hyperuricemia and its correlates in the Russian population (results of ESSE-RF epidemiological study). Rational Pharmacotherapy in Cardiology. 2014;10(2): 153–159. (In Russ.). doi: 10.20996/1819-6446-2014-10-2-153-159
- Lang RM, Bierig M, Devereux RB, et al. Rekomendatsii po kolichestvennoi otsenke struktury i funktsii kamer serdtsa. Russian Journal of Cardiology. 2012;(4S4):1–28.
- Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104. doi: 10.1093/eurheartj/ehy339
- Chazova IE, Oshepkova EV, Zhernakova YuV. Diagnostics and treatment of arterial hypertension. Eurasian heart journal. 2015;(2):3–30. (In Russ.). doi: 10.38109/2225-1685-2015-2-3-30
- Mrochek AG, Atroshchenko ES, Ostrovskii YuP, et al. Natsional'nye rekomendatsii «Diagnostika i lechenie fibrillyatsii predserdii». Minsk; 2010. 84 p. (In Russ.).
- Barysenka TL, Snezhitskiy VA, Kurbat MN, et al. Correlation between hyperuricemia and structural and functional cardiac parameters in patients with hypertension and atrial fibrillation. Journal of the Grodno State Medical University. 2022;20(2):187–196. (In Russ.). doi: 10.25298/2221-8785-2022-20-2-187-196
- Baranova EI. Atrial fibrillation and arterial hypertension. Arterial Hypertension. 2011;17(4):293–304. (In Russ.). doi: 10.18705/1607-419X-2011-17-4-293-304
- Barysenka TL, Snezhitskiy VA. The role of hyperuricemia in the development of atrial fibrillation. Cardiac Arrhythmias. 2021;1(1):7–16. (In Russ.). doi: 10.17816/cardar66609
- Camm AJ, Lip GYH, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation — developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–2747. doi: 10.1093/eurheartj/ehs253
- Zhernakova YuV. Hyperuricemia as risk factor for cardiovascular disease – what’s new? Medical alphabet. 2020;(13):5–11. (In Russ.). doi: 10.33667/2078-5631-2020-13-5-11
- Kepurko TL, Snezhitskiy VA. Hyperuricemia as a risk factor for atrial fibrillation progression. Cardiology in Belarus. 2018;10(1): 125–132. (In Russ.).
- Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013;14:164. doi: 10.1186/1471-2369-14-164
- Maharani N, Kuwabara M, Hisatome I. Hyperuricemia and atrial fibrillation: Possible underlying mechanisms. Int Heart J. 2016;57(4):395–399. doi: 10.1536/ihj.16-192
- Vaziri SM, Larson MG, Lauer MS, et al. Influence of blood pressure on left atrial size. The Framingham Heart Study. Hypertension. 1995;25(6):1155–1160. doi: 10.1161/01.HYP.25.6.1155
- Kuwabara M, Niwa K, Nishihara S, et al. Hyperuricemia is an independent competing risk factor for atrial fibrillation. Int J Cardiol. 2017;231:137–142. doi: 10.1016/j.ijcard.2016.11.268
- Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. Am J Coll Cardiol. 2008;51(8):801–809. doi: 10.1016/j.jacc.2007.09.064
- Jia G, Habibi J, Bostick BP, et al. Uric acid promotes left ventricular diastolic dysfunction in mice fed a Western diet. Hypertension. 2015;65(3):531–539. doi: 10.1161/HYPERTENSIONAHA.114.04737
- Maharani N, Ting YK, Cheng J, et al. Molecular mechanisms underlying urate-induced enhancement of Kv1.5 channel expression in HL-1 atrial myocytes. Circ J. 2015;79(12):2659–2668. doi: 10.1253/circj.CJ-15-0416
- Korantzopoulos P, Letsas K, Fragakis N, et al. Oxidative stress and atrial fibrillation: an update. Free Radic Res. 2018;52 (11-12):1199–1209. doi: 10.1080/10715762.2018.1500696
- Guo Y, Lip GYH, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60(22):2263–2270. doi: 10.1016/j.jacc.2012.04.063
- Karns R, Zhang G, Sun G, et al. Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia. Ann Hum Genet. 2012;76(2):121–127. doi: 10.1111/j.1469-1809.2011.00698.x
- Dehghan A, Kottgen A, Yang Q, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008;372(9654):1953–1961. doi: 10.1016/S0140-6736(08)61343-4