Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.
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SUBMITTER: Rivera-Paredez B
PROVIDER: S-EPMC6627998 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.
Rivera-Paredez Berenice B Macías-Kauffer Luis L Fernandez-Lopez Juan Carlos JC Villalobos-Comparán Marisela M Martinez-Aguilar Mayeli M MM de la Cruz-Montoya Aldo A Ramírez-Salazar Eric G EG Villamil-Ramírez Hugo H Quiterio Manuel M Ramírez-Palacios Paula P Romero-Hidalgo Sandra S Villarreal-Molina María Teresa MT Denova-Gutiérrez Edgar E Flores Yvonne N YN Canizales-Quinteros Samuel S Salmerón Jorge J Velázquez-Cruz Rafael R
Nutrients 20190614 6
Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide association study GWAS was performed in a subgroup of participants (<i>n</i> = 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (<i>n</i> = 1939) and replicated in independent childre ...[more]
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Project description:ObjectiveAdipose tissue plays a crucial role in serum uric acid (UA) metabolism, but the relative contribution of adipose tissue insulin resistance (IR) to serum UA levels and hyperuricemia have not explicitly been illustrated. Herein, we aimed to investigate the association between the adipose tissue insulin resistance index (Adipo-IR) and hyperuricemia in this cross-sectional study. The homeostasis model assessment of insulin resistance (HOMA-IR) index, another widely applied marker to determine systemic IR, was also explored.MethodsA total of 5821 adults were included in this study. The relationship between Adipo-IR or HOMA-IR and serum UA levels was assessed by multivariate linear regression. Binary logistic regression analyses were applied to determine the sex-specific association of the Adipo-IR tertiles and HOMA-IR tertiles with hyperuricemia. Participants were then divided into normal BMI (18.5 ≤ BMI < 24) and elevated BMI (BMI ≥ 24) groups for further analysis.ResultsBoth Adipo-IR and HOMA-IR were positively correlated with serum UA (P < 0.001). Compared with the lowest tertile, the risks of hyperuricemia increased across Adipo-IR tertiles (middle tertile: OR 1.52, 95%CI 1.24-1.88; highest tertile: OR 2.10, 95%CI 1.67-2.63) in men after full adjustment (P for trend < 0.001). In women, only the highest tertile (OR 2.09, 95%CI 1.52-2.87) was significantly associated with hyperuricemia. Those associations remained significant in participants with normal BMI status. As for HOMA-IR, only the highest tertile showed positive relationships with hyperuricemia in both genders after full adjustment (P for trend < 0.001). The association between HOMA-IR and hyperuricemia disappeared in men with normal BMI status.ConclusionsAdipo-IR was strongly associated with serum UA and hyperuricemia regardless of BMI classification. In men with normal BMI, Adipo-IR, rather than HOMA-IR, was closely associated with hyperuricemia. Altogether, our finding highlights a critical role of adipose tissue IR on serum UA metabolism and hyperuricemia.
| S-EPMC9226335 | biostudies-literature
Project description:Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P?=?8.3?×?10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P?=?6.7?×?10(-19); risk ratio?=?0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42?mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89?mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction?=?1.5?×?10(-12)).
| S-EPMC4731750 | biostudies-literature
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.
| S-EPMC4793330 | biostudies-literature
Project description:BackgroundWe aimed to assess the differences in the gut microbiome among participants with different uric acid levels (hyperuricemia [HUA] patients, low serum uric acid [LSU] patients, and controls with normal levels) and to develop a model to predict HUA based on microbial biomarkers.MethodsWe sequenced the V3-V4 variable region of the 16S rDNA gene in 168 fecal samples from HUA patients (n=50), LSU patients (n=61), and controls (n=57). We then analyzed the differences in the gut microbiome between these groups. To identify gut microbial biomarkers, the 107 HUA patients and controls were randomly divided (2:1) into development and validation groups and 10-fold cross-validation of a random forest model was performed. We then established three diagnostic models: a clinical model, microbial biomarker model, and combined model.ResultsThe gut microbial α diversity, in terms of the Shannon and Simpson indices, was decreased in LSU and HUA patients compared to controls, but only the decreases in the HUA group were significant (P=0.0029 and P=0.013, respectively). The phylum Proteobacteria (P<0.001) and genus Bacteroides (P=0.02) were significantly increased in HUA patients compared to controls, while the genus Ruminococcaceae_Ruminococcus was decreased (P=0.02). Twelve microbial biomarkers were identified. The area under the curve (AUC) for these biomarkers in the development group was 84.9% (P<0.001). Notably, an AUC of 89.1% (P<0.001) was achieved by combining the microbial biomarkers and clinical factors.ConclusionsThe combined model is a reliable tool for predicting HUA and could be used to assist in the clinical evaluation of patients and prevention of HUA.
| S-EPMC9553226 | biostudies-literature
Project description:BackgroundUric acid (UA) is the end product of purine metabolism in the liver and is excreted by the kidneys. When purine metabolism is impaired, the serum UA level will be elevated (hyperuricemia) and eventually lead to gout. During evolution, humans and some primates have lost the gene encoding uricase, which is vital in UA metabolism. With the advances of human society, the prevalence of hyperuricemia has dramatically increased because of the refined food culture. Hyperuricemia can be controlled by drugs, such as allopurinol and probenecid. However, these drugs have no preventive effect and are associated with unpleasant side effects. An increasing number of probiotic strains, which are able to regulate host metabolism and prevent chronic diseases without harmful side effects, have been characterized. The identification of probiotic strains, which are able to exert beneficial effects on UA metabolism, will provide an alternative healthcare strategy for patients with hyperuricemia, especially for those who are allergic to anti-hyperuricemia drugs.MethodsTo elicit hyperuricemia, rats in the symptom control group (HP) were injected with potassium oxonate and fed a high-purine diet. Rats in the probiotic groups received the high-purine diet, oxonate injection, and supplements of probiotic strains TSR332, TSF331, or La322. Rats in the blank control group (C) received a standard diet (AIN-93G) and oxonate injection.ResultsPurine-utilizing strains of probiotics were screened using high-pressure liquid chromatography (HPLC) in vitro, and the lowering effect on serum UA levels was analyzed in hyperuricemia rats in vivo. We found that Lactobacillus reuteri strain TSR332 and Lactobacillus fermentum strain TSF331 displayed significantly strong assimilation of inosine (90%; p = 0.00003 and 59%; p = 0.00545, respectively) and guanosine (78%; p = 0.00012 and 51%; p = 0.00062, respectively) within 30 min in vitro. Further animal studies revealed that serum UA levels were significantly reduced by 60% (p = 0.00169) and 30% (p = 0.00912), respectively, in hyperuricemic rats treated with TSR332 and TSF331 for 8 days. Remarkably, TSR332 ameliorated the occurrence of hyperuricemia, and no evident side effects were observed. Overall, our study indicates that TSR332 and TSF331 are potential functional probiotic strains for controlling the development of hyperuricemia.
| S-EPMC8101448 | biostudies-literature
Project description:ObjectiveUric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.MethodsThe cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.ResultsThe models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.ConclusionMetabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.
| S-EPMC4020828 | biostudies-literature
Project description:ObjectivesDiabetes and other metabolic diseases have been linked to the development of periodontitis, but little research has been done to determine whether serum uric acid (SUA) levels and hyperuricemia play a role. This study aimed to investigate the relationship between SUA, hyperuricemia, and periodontitis.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we created a nationally representative data set. We used multivariable logistic regression models to assess the relationship between SUA, hyperuricemia, and periodontitis and presented odds ratios (OR) in women and men, respectively.ResultsIn women, adjusted multivariable regression models showed that SUA (4.1-4.3mg/dl) was associated with higher odds of periodontitis (OR = 1.43; 95% confidence interval (CI):1.0 ~ 2.03, p = 0.047) with SUA (≤ 3.3mg/dl) as reference. The risk of periodontitis tended to increase slightly but insignificantly with increasing SUA levels, and the adverse effects occurred only when SUA increased to a certain level, and then reached a plateau. In men, the adjusted OR values for SUA (4.9-5.2mg/dl), SUA (5.3-5.5mg/dl), SUA (5.9-6.2mg/dl), and SUA (6.3-6.5mg/dl) were 0.66 (95% CI: 0.45 ~ 0.96, p = 0.029), 0.58 (95% CI: 0.40 ~ 0.85, p = 0.006), 0.67(95% CI: 0.47 ~ 0.97, p = 0.035), and 0.67 (95% CI: 0.45 ~ 0.99, p = 0.043), respectively, with SUA (≤ 4.3mg/dl) as reference. The elevated SUA levels are protective against periodontitis, but there is a range within which the risk of periodontitis decreases, followed by a non-significant tendency to increase.ConclusionsThe levels of SUA that are linked to the risk of periodontitis. Future prospective longitudinal studies and strategies are required to further confirm whether controlled SUA treatment is an effective adjunct to systematic periodontal therapy and whether SUA can be used as a diagnostic biomarker to assess the risk or progression of periodontitis.
| S-EPMC10466695 | biostudies-literature
Project description:Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age x sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean +/- SD serum uric acid for all individuals was 5.14 +/- 1.5 mg/dl. Serum uric acid was found to be significantly heritable (0.46 +/- 0.03 in all centers, and 0.39 +/- 0.07, 0.51 +/- 0.05, 0.44 +/- 0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations.
| S-EPMC2784272 | biostudies-literature
Project description:Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single-artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010-2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle-brachial index (ABI) on January 2010 and January 2012 based on regular health check-ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on-set vascular stenosis due to hyperuricaemia and a 1-mg/dL change in SUA level were 1.75 (1.32-2.31) and 1.29 (1.21-1.38), respectively. Furthermore, in the gender-stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18-3.46), but not females (OR: 0.85, 95% CI: 0.41-1.76, P for interaction: 0.026).
| S-EPMC6652300 | biostudies-literature
Project description:AimsHyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19.MethodsThis was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19.ResultsSUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group.ConclusionPatients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.
| S-EPMC8106517 | biostudies-literature