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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: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.

Project description:IntroductionThe current study sought to explore the effect of baseline serum uric acid (SUA) on the risk of all-cause mortality among Chinese adults aged 45~75 years and to determine its interaction relationship with diabetes.MethodsThe study was designed as a community-based cohort of 4467 adults aged between 45~75 years included in a 6-years follow-up period from 2009 to 2015 years by the China Health and Nutrition Survey (CHNS). Baseline SUA levels were grouped into quartiles and its association on all-cause mortality was explored using multivariate Cox proportional hazards models. Stratified analyses were performed to explore the associations of SUA quartiles with all-cause mortality among diabetic and non-diabetic individuals.ResultsA total of 141 deaths (5.3 per 1000 person-years) were recorded During a follow-up of 26431 person-years. Out of the 141 deaths, 28 deaths (10.1 per 1000 person-years) were reported in the diabetic groups and 113 deaths (4.8 per 1000 person-years) were recorded in the non-diabetic group. An increased risk of all-cause mortality was observed for participants in the first and fourth quartiles compared with the second SUA quartile, (Q1 SUA: aHR=2.1, 95% CI 1.1~4.1; Q4 SUA: aHR=2.1, 95% CI 1.1~4.0). Stratification of participants by diabetes status showed a U-shaped association for non-diabetic individuals. Whereas, declined eGFR, rather than SUA, was an independent risk factor for all-cause mortality in diabetic individuals (aHR=0.7, 95% CI 0.6~1.0).ConclusionOur study proved that the prognostic role of SUA for predicting all-cause death might be regulated by diabetes. Both low and high SUA levels were associated with increased mortality, supporting a U-shaped association only in non-diabetic individuals. Whereas, renal dysfunction rather than SUA was an independent risk factor for all-cause mortality. Further studies should be conducted to determine the SUA levels at which intervention should be conducted and explore target follow-up strategies to prevent progression leading to poor prognosis.

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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