Genome Scan for Determinants of Serum Uric Acid Variability

Nath, Subrata Deb; Voruganti, V. Saroja; Arar, Nedal H.; Thameem, Farook; López-Alvarenga, Juan Carlos; Bauer, Richard L.; Blangero, John; MacCluer, Jean W.; Comuzzie, Anthony G.; Abboud, Hanna E.

doi:10.1681/asn.2007040426

Cited by 78 publications

(58 citation statements)

References 45 publications

(43 reference statements)

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“…Most studies report heritability estimates of about 40%. [13][14][15] Recently, a large meta-analysis including .140,000 individuals identified 28 genetic loci that were significantly associated with serum UA concentration genome wide 16 and explained about 7% of its variation. This knowledge of the genetic regulation of UA allows the use of MR to examine a possible causal relationship between UA and cardiovascular risk.…”

mentioning

confidence: 99%

Uric Acid and Cardiovascular Events

Kleber

Delgado

Grammer

et al. 2015

Journal of the American Society of Nephrology

224

140

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Obesity and diets rich in uric acid-raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid-regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.

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mentioning

confidence: 99%

Uric Acid and Cardiovascular Events

Kleber

Delgado

Grammer

et al. 2015

Journal of the American Society of Nephrology

224

140

View full text Add to dashboard Cite

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“…Although conventional factors, including age, body mass index (BMI), alcohol consumption and cigarette smoking, contribute greatly to variations in SUA concentrations [27], genetic determinants also play roles, and heritability as high as 42% have been reported [28]. Moreover, genetic studies facilitate the development of effective treatments for associated diseases.…”

Section: Genetic Predisposition To Hyperuricemiamentioning

confidence: 99%

Genes associated with metabolic syndrome and hyperuricemia: An overview

Pokharel¹,

Acharya²,

Chowdhury³

2015

Clin Case Rep Rev

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Purposes:Recently, different studies have found genetic basis for hyperuricemia, metabolic syndrome and different components of it. The purpose of our review is to overview the different genes that have been studied with regard to hyperuricemia, metabolic syndrome and its components. Method:We made this review by systematically searching relevant literatures using multiple keywords and standardized terminology on PubMed, Nature.com, Hindawi.com, Plosone.com etc and other online resources related to the topic of our study. Findings:Serum uric acid level is influenced by diet, cellular breakdown, renal elimination and correlates with metabolic syndrome, diabetes mellitus, blood pressure, gout, and cardiovascular disease. Metabolic syndrome has strong association with the development of type II diabetes and risk of cardiovascular morbidity and mortality.We found associations of different genes regarding hyperuricemia, metabolic syndrome and its components like diabetes mellitus, obesity, dyslipidemia, and hypertension.Conclusions: This review provides evidence that different genes are responsible for the causation of Metabolic syndrome and its each component. Further genetic studies with different population groups and races in different parts of the world need to be carried out to find specific relation and effect of each gene in each specific component of our study.

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“…In addition, it is linked to insulin resistance, type 2 diabetes, metabolic syndrome and obesity [3][4][5][6] . Although conventional factors, including age, body mass index (BMI), alcohol consumption and cigarette smoking, contribute greatly to variations in serum uric acid concentrations [7][8][9][10][11] , genetic determinants also play roles, and heritabilities as high as 42% have been reported [12] . Moreover, genetic studies facilitate the development of effective treatments for associated diseases [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population

et al. 2014

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Aim: Genome-wide association studies have identified several novel loci associated with serum uric acid concentrations in individuals of European descent. In the current study, we aimed to evaluate the associations between these loci and serum uric acid concentrations in a Chinese population. Methods: Fourteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped in 2329 Chinese subjects in Shanghai. Serum biochemical parameters including uric acid concentrations were determined. All the variants were analyzed for gender differences since uric acid metabolism differed between genders. Results: In males after adjustments for age and BMI, GCKR rs780094, SLC2A9 rs11722228 and SF1 rs606458 were associated with the uric acid concentrations, which were statistically significant (P=0.016, 0.001 and 0.03, respectively), whereas SLC2A9 rs3775948 was marginally associated with the uric acid concentrations (P=0.071). In females, SLC22A12 rs506338 was also marginally associated with the uric acid concentrations (P=0.057). The meta-analysis for combined data from both males and females revealed that rs3775948 and rs606458 were associated with the uric acid concentrations (P=0.036 and 0.043, respectively). Furthermore, the gender significantly affected the association of rs11722228 with serum uric acid levels (P=0.012). Conclusion: The SLC2A9 rs11722228, SF1 rs606458 and GCKR rs780094 variants modulate uric acid concentrations in Chinese males, while SF1 rs606458 and SLC2A9 rs3775948 are associated with the uric acid concentrations in both Chinese males and females.

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Genome Scan for Determinants of Serum Uric Acid Variability

Cited by 78 publications

References 45 publications

Uric Acid and Cardiovascular Events

Uric Acid and Cardiovascular Events

Genes associated with metabolic syndrome and hyperuricemia: An overview

Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population

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