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Dysfunctional ABCG2 gene polymorphisms are associated with serum uric acid levels and all-cause mortality in hemodialysis patients.

ABSTRACT: Dysfunctional variants of ATP-binding cassette transporter subfamily G member 2 (ABCG2), a urate transporter in the kidney and intestine, are the major causes of hyperuricemia and gout. A recent study found that ABCG2 is a major transporter of uremic toxins; however, few studies have investigated the relationship between ABCG2 gene polymorphisms and mortality. This prospective cohort study of 1214 hemodialysis patients investigated the association between serum uric acid levels and ABCG2 genotype and mortality. Genotyping of dysfunctional ABCG2 variants, Q126X (rs72552713) and Q141K (rs2231142), was performed using the patients' DNA. During the study period, 220 patients died. Lower serum uric acid levels were associated with higher mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.14-3.10, P???0.001). ABCG2 dysfunction, estimated by genetic variants, had a significant positive association with serum uric acid levels (full function: 7.4?±?1.2 mg/dl, 3/4 function: 7.9?±?1.3 mg/dl, 1/2 function: 8.2?±?1.4 mg/dl, ??1/4 function: 8.7?±?1.3 mg/dl, P???0.001). This association remained significant on multiple regression analysis. The Cox proportional hazard analysis indicated that the ABCG2???1/4 function type was significantly associated with higher mortality (HR 6.66, 95% CI 2.49 to 17.8, P???0.001) than the other function types. These results showed that ABCG2 plays a physiologically important role in uric acid excretion, and that ABCG2 dysfunction is a risk factor for mortality in hemodialysis patients.

SUBMITTER: Nakashima A

PROVIDER: S-EPMC7324430 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Dysfunctional ABCG2 gene polymorphisms are associated with serum uric acid levels and all-cause mortality in hemodialysis patients.

Nakashima Akio A Ichida Kimiyoshi K Ohkido Ichiro I Yokoyama Keitaro K Matsuo Hirotaka H Ohashi Yuki Y Takada Tappei T Nakayama Akiyoshi A Suzuki Hiroshi H Shinomiya Nariyoshi N Urashima Mitsuyoshi M Yokoo Takashi T

Human cell 20200316 3

Dysfunctional variants of ATP-binding cassette transporter subfamily G member 2 (ABCG2), a urate transporter in the kidney and intestine, are the major causes of hyperuricemia and gout. A recent study found that ABCG2 is a major transporter of uremic toxins; however, few studies have investigated the relationship between ABCG2 gene polymorphisms and mortality. This prospective cohort study of 1214 hemodialysis patients investigated the association between serum uric acid levels and ABCG2 genotyp ...[more]

PMID: 32180207

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Project description:BackgroundElderly hemodialysis patients have a higher rate of mortality than nonelderly hemodialysis patients. Recent studies shown that the serum uric acid to creatinine ratio (SUA/Scr) was associated with all-cause mortality in general adults. The purpose of the present study was to investigate the association between the SUA/Scr and all-cause and cardiovascular disease mortality among elderly hemodialysis patients.MethodsA total of 222 patients (≥ 60 years) who received hemodialysis more than 8 h per week at Taizhou Second People's Hospital for at least 3 months were enrolled in the present study from January 2015 to December 2019. Clinical characteristics including age, sex and height et. al, were obtained from the hemodialysis database. The laboratory data, including albumin (ALB), total cholesterol (TC), serum uric acid (SUA), serum creatinine (Scr) and so on, were collected before hemodialysis and analyzed by automatic biochemical analyzer. Survival information was recorded during the follow-up period. Multiple Cox regression was carried out to analyze the association between SUA/Scr and all-cause mortality. The survival rate of each group was calculated by the Kaplan-Meier method, and the ratio of survival curves was analyzed by the log-rank test. The contribution of SUA/Scr for predicting all-cause mortality risk was evaluated by net reclassification improvement (NRI).ResultsDuring the 19-month observation period, 78 patients died. Individuals in the nonsurviving group had significantly older ages (P < 0.001), body mass index (BMI) (P = 0.004), serum creatinine (P = 0.005) and prealbumin (P = 0.006) than surviving patients. After adjusting for age, sex, BMI, prealbumin, dialysis vintage, dialysis frequency, single-pool Kt/V (spKt/V), DM, hypertension and comorbidities, a higher ratio of SUA/Scr was independently associated with a higher risk of all-cause mortality (HR: 1.292; 95% CI: 1.013-1.648; P = 0.039). The predict value on all-cause mortality of SUA/Scr was superior to SUA (additive NRI = 0.214, P = 0.015) and Scr (additive NRI = 0.476, P < 0.001) among elderly hemodialysis patients.ConclusionThe serum uric acid to creatinine ratio is strongly associated with all-cause mortality in elderly hemodialysis patients which is more predictive than SUA or Scr alone.

Project description:Objective:There is no consensus on the role of abnormal uric acid (UA) levels in the prognosis of patients undergoing hemodialysis. We therefore aimed to investigate the effects of changes in UA concentration on the risk of all-cause death and cardiac death in such patients. Method:In this retrospective cohort study, patients admitted to two hemodialysis centers performing maintenance hemodialysis (MHD) in Wuhan First Hospital and Fourth Hospital Hemodialysis Center from January 1, 2007, to October 31, 2017, were included. Results:In all, 325 patients undergoing MHD aged 59.7 ± 14.7 years, including 195 men (60%), were enrolled, with a median follow-up of 37 months. Serum UA (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (. Conclusion:Low UA levels were closely related to all-cause mortality in patients undergoing MHD. Although UA levels had no significant effect on cardiac death, they had a good predictive value for long-term prognosis in patients on MHD.

Project description:Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18-69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions.

Dataset Information

Dysfunctional ABCG2 gene polymorphisms are associated with serum uric acid levels and all-cause mortality in hemodialysis patients.

Publications

Dysfunctional ABCG2 gene polymorphisms are associated with serum uric acid levels and all-cause mortality in hemodialysis patients.

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