Differential gene expression of ABCG2, SLC22A12, IL-1β, and ALPK1 in peripheral blood leukocytes of primary gout patients with hyperuricemia and their comorbidities: a case-control study.

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.