SLC2A9 Genotype Distribution and Left Atrium Diameter in Patients with Arterial Hypertension and Atrial Fibrillation

V. Snezhitskiy, A. Kopytsky, Tatyana L. Barysenkо (Kepurko)
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引用次数: 0

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 anteriorposterior 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 Pearsons test. The KruskalWallis 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 2 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).
SLC2A9基因型分布与高血压和心房颤动患者左心房直径的关系
背景:近年来,无症状高尿酸血症(HU)被发现对心血管系统有显著的不良影响。尿酸(UA)在心肌细胞的积累可引起心房的离子和结构重塑。UA升高的原因之一和HU的重要危险因素是SLC2A9基因的多态性,该基因编码GLUT9蛋白,这是近端肾小管细胞中高度特异性的尿酸转运蛋白。目的:探讨动脉性高血压(AHT)合并心房颤动(AF)患者SLC2A9基因rs734553多态性基因型及等位基因频率与左心房(LA)直径的关系。材料与方法:104例患者,男性94例(90.4%),女性10例(9.6%)(55岁[45;[61]岁)被纳入研究。患者分为以下组:首次AF患者(n = 13);第二例合并AHT和AF的患者(n = 68);第三例为AHT患者(n = 23)。经胸超声心动图显示的左室直径等于左室前后尺寸作为左室结构改变的特征。所有患者均接受仪器、实验室和分子基因检测,包括使用聚合酶链反应技术进行SLC2A9基因rs734553多态性检测。数据以中位数、第一和第三四分位数以及绝对和相对频率表示。采用Mann Whitney u型检验和Fisher & pearson检验评估两组患者之间的差异。KruskalWallis检验用于比较三个独立的组。p 0.05认为差异有统计学意义。定量变量和二分类变量之间的关系用秩-双列相关系数(rrb)来描述。采用Hardy Weinberg平衡法检测各组患者的等位基因和基因型分布,并采用2检验进行评估。结果:两组患者LA直径及SLC2A9基因rs734553多态性基因型比较,差异均无统计学意义(p < 0.05)。然而,在组2中,CC基因型的LA直径(43 [42;44] mm)和AC基因型(40 [49;43] mm)的患者比AA基因型患者(38 [38;42毫米)。第1组AC基因型患者的LA直径(40 [38;42] mm)大于AA基因型(38 [34;38毫米)。在研究LA扩张患者SLC2A9基因rs734553多态性基因型及等位基因分布频率时,我们发现在第二组患者中,AC基因型明显多于其他组(23.5%)(p = 0.004), AA基因型(13.2%)和CC基因型(14.7%)的发生率也有较高的趋势。但未达到统计学显著性标准。值得注意的是,在第一组患者中,LA扩张仅被诊断为AC基因型(38.5%)。第三组患者未见LA扩张。结论:在第1组(AF)患者中,仅AC基因型患者出现LA扩张。在第2组(合并AHT和AF)患者中,AC基因型患者的LA扩张频率明显更高(p = 0.004)。SLC2A9基因rs734553多态性的AC和CC基因型在2组患者(AHT和AF)中更为常见。
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