Dataset Information

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.

ABSTRACT:

Background

Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children.

Objective

The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study.

Design

We conducted a genomewide association study with 1.1 million genetic markers in 815 children.

Results

We found serum uric acid to be significantly heritable [h(2) ± SD = 0.45 ± 0.08, P = 5.8 × 10(-11)] and associated with SLC2A9 variants (P values between 10(-16) and 10(-7)). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001).

Conclusions

Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children.

SUBMITTER: Voruganti VS

PROVIDER: S-EPMC4381775 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.

Voruganti V Saroja VS Laston Sandra S Haack Karin K Mehta Nitesh R NR Cole Shelley A SA Butte Nancy F NF Comuzzie Anthony G AG

The American journal of clinical nutrition 20150128 4

<h4>Background</h4>Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children.<h4>Objective</h4>The aim was to investigate whether variation in serum uric ...[more]

PMID: 25833971

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Project description:ObjectiveThe role of diet quality and nutrient adequacy in the etiology of childhood obesity is poorly understood. The specific aims of these analyses were to assess overall diet quality and nutrient adequacy, and test for association between weight status and diet in children from low socioeconomic status (SES) Hispanic families at high risk for obesity.DesignA cross-sectional study design was used to assess dietary intake in low-SES Hispanic children with and without overweight who were enrolled in the Viva la Familia Study. Multiple-pass 24-hour dietary recalls were recorded on two random, weekday occasions. Diet quality was evaluated according to the Dietary Guidelines for Americans. Nutrient adequacy was assessed using z scores based on estimated average requirement or adequate intake.Subjects/settingThe study included 1,030 Hispanic children and adolescents, aged 4 to 19 years, in Houston, TX, who participated between November 2000 and August 2004.Statistical analysisSTATA software (version 9.1, 2006, STATA Corp, College Station, TX) was used for generalized estimating equations and random effects regression.ResultsDiet quality did not adhere to the Dietary Guidelines for Americans for fat, cholesterol, saturated fatty acids, fiber, added sugar, and sodium. Although energy intake was significantly higher in children with overweight, food sources, diet quality, macro- and micronutrient composition were similar between non-overweight and overweight children. Relative to estimated average requirements or adequate intake levels, mean nutrient intakes were adequate (70% to 98% probability) in the children without and with overweight, except for vitamins D and E, pantothenic acid, calcium, and potassium, for which z scores cannot be interpreted given the uncertainty of their adequate intake levels.ConclusionsWhereas the diets of low-SES Hispanic children with and without overweight were adequate in most essential nutrients, other components of a healthful diet, which promote long-term health, were suboptimal. Knowledge of the diets of high-risk Hispanic children will inform nutritional interventions and policy.

Project description:ObjectivesSLC2A9 gene variants have been associated with urinary uric acid (UA) concentration, but little is known about the functional mechanism linking these gene variants with UA. SLC2A9 encodes a UA transporter present in the proximal tubule of the kidney, and gene expression levels of SLC2A9 and other genes in the uricosuric pathway (ABCG2, SLC17A1, SLC17A3, and SLC22A12) could potentially mediate the relationship between SLC2A9 gene variants and urinary UA excretion.MethodsThe association between urinary UA concentrations and single nucleotide polymorphisms (SNPs) within the SLC2A9 gene region, expression levels of genes in the uricosuric pathway, and dietary protein intake were analyzed for a sample of non-Hispanic white participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort. The SLC2A9 SNP most significantly associated with urinary UA concentration was then tested for associations with gene expression levels from uric acid absorption/secretion associated genes. Models including interactions between dietary protein (total, animal, and vegetable) and genetic factors were also assessed.ResultsThe most significant SLC2A9 SNP associated with urinary UA (rs12509955, corrected p = 0.001) was also associated with SLC2A9 gene expression levels (corrected p = 0.0084); however, SLC2A9 gene expression levels were not significantly associated with urinary UA concentrations (p = 0.509). The interactions between rs12509955 and total dietary protein, and SLC2A9 gene-level gene expression and dietary vegetable protein on the outcome of urinary UA were marginally significant (p = 0.11 and p = 0.07, respectively). Gene expression level of one SLC2A9 transcript had a significant interaction with dietary animal protein (SLC2A9-001 ENST00000506583, p = 0.01) and a marginally significant interaction with total dietary protein (p = 0.07) on urinary UA.ConclusionOur results illustrate that SNPs in the SLC2A9 gene influence SLC2A9 gene expression as well as urinary UA excretion. Evidence is also suggestive that gene-by-diet interactions may disproportionately increase urinary UA in genetically susceptible individuals that consume higher amounts of protein.

Dataset Information

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.

Background

Objective

Design

Results

Conclusions

Publications

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.

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