Gout

MacFarlane, Lindsey A.; Kim, Seo Young

doi:10.1016/j.rdc.2014.07.002

Cited by 87 publications

(33 citation statements)

References 144 publications

(156 reference statements)

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“…Gout is often divided into primary gout and secondary gout. Secondary gout is more common and is mainly caused by life style factors, pharmaceutical treatments or other diseases [6, 7]. The prevalence of gout has gradually increased over the last decades [8].…”

Section: Introductionmentioning

confidence: 99%

Seasonal variations of urate in a Swedish adult population

et al. 2017

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Seasonality in the incidence and prevalence of gout has previously been reported but the cause of this seasonality in gout is not explained. The aim of this study was to evaluate possible seasonal variations of urate in a large unselected Swedish adult population. We analyzed 170,915 urate test results from patients at a tertiary care hospital between 2000 and 2016. The results were divided according to sex and sampling month of the year. The median urate values were overall higher in males compared to females and both males and females had peak urate concentrations in the summer months (June–August). There is a seasonal pattern for urate concentrations in a large Swedish population similar to the previously reported seasonality for gout. This may be clinically important and could contribute to the circannual variation of gout. The seasonal pattern should be recognized when evaluating patient results both in clinical practice and in research studies.

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Section: Introductionmentioning

confidence: 99%

Seasonal variations of urate in a Swedish adult population

et al. 2017

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“…Hyperuricemia is also an important risk factor for cardiovascular, renal, and metabolic diseases [ 5 – 9 ]. Studies suggest that besides several non-modifiable risk factors like genetics, race, sex, and age, some modifiable risk factors such as diet and lifestyle are also associated with gout [ 10 ]. Increased prevalence of hyperuricemia, use of low-dose aspirin, occurrence of obesity and metabolic syndrome, alcohol consumption, longevity, rampant use of diuretics, and dietary trends are all contributing factors to the increased prevalence of gout, especially in developed countries [ 11 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food

et al. 2016

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Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a combination of engineered KlacPNP and other enzymes involved in purine degradation could effectively lower the purine content in foods and beverages.

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“…Accumulated evidences have implied that monosodium urate (MSU) crystal-induced inflammation is a paradigm of innate immunity and NALP3 inflammasome is involved in gout development [8,9,10]. NALP3 inflammasome contains NALP3, apoptosis-associated speck (ASC)-like protein and caspase activation and recruitment domain 8 (CARD8) [11,12].…”

Section: Introductionmentioning

confidence: 99%

CARD8 rs2043211 Polymorphism is Associated with Gout in a Chinese Male Population

Chen

Ren

et al. 2015

Cell Physiol Biochem

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Background &Aim: Previous studies have suggested genetic factors are involved in the development of gout. We performed a case-control study to investigate the genetic association between CARD8 rs2043211 polymorphism and gout. Methods: A total of 396 male patients with gout and 403 age- and sex- matched healthy controls were included in this study. Genotyping was performed using TaqMan SNP Genotyping Assays. An association analysis was carried out using the χ2 test. The genotype-phenotype analysis was also conducted. Results: The genotype distribution of CARD8 rs2043211 polymorphism confirmed to HWE in the controls (P = 0.27). There was an obvious difference in the genotype distribution of CARD8 rs2043211 polymorphism between cases and controls (P = 0.017). In addition, there was an obvious association between CARD8 rs2043211 polymorphism and gout under the recessive comparison model (AA vs. TT/TA: OR = 0.65, 95%CI 0.47-0.88, P = 0.006). Patients carrying genotype TT of CARD8 rs2043211 polymorphism had higher triglycerides levels compared to those carrying the AA genotype (2.77±2.08 mmol/L vs. 2.07±1.15 mmol/L, P = 0.01). Patients with the TT genotype also had significantly higher systolic blood pressure compared with those with the AA genotype (142.11±21.10 mmHg vs. 135.38±14.66 mmHg, P = 0.03). Patients carrying TT genotype also had an increased risk of renal calculus compared with those carrying the AA genotype. Conclusion: CARD8 rs2043211 polymorphism is significantly associated with susceptibility to gout in Chinese Han males.

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Gout

Cited by 87 publications

References 144 publications

Seasonal variations of urate in a Swedish adult population

Seasonal variations of urate in a Swedish adult population

Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food

CARD8 rs2043211 Polymorphism is Associated with Gout in a Chinese Male Population

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