背景:ABCG2、SLC22A12和ALPK1基因与痛风患者尿酸代谢功能障碍密切相关,但尚不清楚这些转运体如何在急性或慢性痛风患者中表达。我们的目标是:(a)分析痛风患者和对照组外周血中尿酸盐转运体和炎症基因的基因表达;(b)确定痛风患者的代谢谱是否可以影响尿酸盐转运体的基因表达谱和表达。ABCG2和SLC22A12,以及炎症分子,ALPK1和IL-1β,痛风患者外周血白细胞;(c)将它们与没有痛风和没有高尿酸血症的人的代谢谱和基因表达进行比较。
方法:共纳入36例慢性和急性患者和52例对照,和ABCG2,SLC22A12,IL-1β,通过实时定量PCR评估ALPK1基因的表达。还分析了基因表达与患者临床和实验室参数的相关性。
结果:患者外周血单核细胞(PBMC)中的IL-1β与多形核白细胞白细胞(PMNLs,p<0.05)。与对照组相比,在来自患者的PMNLs中发现ABCG2和IL-1β显著增加(p<0.05)。发现患者的基因表达与血清尿酸(sUA)水平相关,血清肌酐,C反应蛋白(CRP),甘油三酯,体重指数(BMI),肾病,高血压,和代谢综合征。
结论:我们的数据表明,患者的白细胞对高尿酸血症和合并症的存在有反应,ABCG2和IL-1β基因的表达与正常贫血和非疾病状态相比有差异。高尿酸血症,血脂异常,肥胖可能刺激外周血白细胞(中性粒细胞和单核细胞)的差异基因表达,即使处于无症状状态。
BACKGROUND: The ABCG2,
SLC22A12, and ALPK1 genes have been strongly associated with dysfunction of urate metabolism in patients with gout, but it is unknown how these transporters are expressed in patients with acute or chronic gout. Our objectives were to: (a) analyze the gene expression of urate transporters and of inflammation genes in peripheral blood from gout patients and controls; (b) determine whether the metabolic profile of gout patients can influence the gene expression profile and the expression of urate transporters, ABCG2 and
SLC22A12, and inflammation molecules, ALPK1 and IL-1β, in peripheral blood leukocytes from gout patients; (c) compare them with their metabolic profile and the gene expression of people without gout and without hyperuricemia.
METHODS: A total of 36 chronic and acute patients and 52 controls were recruited, and ABCG2,
SLC22A12, IL-1β, and ALPK1 gene expression was evaluated by quantitative real-time PCR. Correlations of gene expression with clinical and laboratory parameters of patients were also analyzed.
RESULTS: IL-1β was significantly increased in peripheral blood mononuclear cells (PBMCs) of patients compared with their polymorphonuclear leukocytes white blood cells (PMNLs, p < 0.05). A significant increase in ABCG2 and IL-1β was found in PMNLs from patients compared to controls (p < 0.05). Correlations of gene expression in patients were found with levels of serum uric acid (sUA), serum creatinine, C-reactive protein (CRP), triglycerides, body mass index (BMI), kidney disease, hypertension, and metabolic syndrome.
CONCLUSIONS: Our data suggest that leukocytes of patients respond to the presence of hyperuricemia and comorbidities, expressing ABCG2 and IL-1β genes differentially compared to normouricemic and nondisease states. Hyperuricemia, dyslipidemia, and obesity probably stimulate the differential gene expression of peripheral blood leukocytes (neutrophils and monocytes), even in an asymptomatic state.