Dataset Information

Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease.

ABSTRACT: We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients. Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined. Interactions of urate-associated variants with urate-altering medications and clinical characteristics of gout were evaluated. Genome-wide significant associations with serum urate and gout were identified for known loci at SLC2A9 and ABCG2, but not for novel loci. Effects of the 26 known SNPs were of similar magnitude in CKD patients compared to population-based individuals, except for SNPs at ABCG2 that showed greater effects in CKD. Gene-medication interactions were not significant when accounting for multiple testing. Associations with gout in specific joints were significant for SLC2A9 rs12498742 in wrists and midfoot joints. Known genetic variants in SLC2A9 and ABCG2 were associated with urate and gout in a CKD cohort, with effect sizes for ABCG2 significantly greater in CKD compared to the general population. CKD patients are at high risk of gout due to reduced kidney function, diuretics intake and genetic predisposition, making treatment to target challenging.

SUBMITTER: Jing J

PROVIDER: S-EPMC6123425 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease.

Jing Jiaojiao J Ekici Arif B AB Sitter Thomas T Eckardt Kai-Uwe KU Schaeffner Elke E Li Yong Y Kronenberg Florian F Köttgen Anna A Schultheiss Ulla T UT

Scientific reports 20180904 1

We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients. Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined. Interactions of urate-associated variants with urate-altering medications and clinical ...[more]

PMID: 30181573

Similar Datasets

Project description:BackgroundPrevious studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.MethodsData was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2-4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL).ResultsMean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA < 6.0 (n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0-6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement.ConclusionSingle sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of < 6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point.Trial registrationData from parent study ClinicalTrials.gov Identifier: NCT02038179 .

Dataset Information

Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease.

Publications

Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets