西班牙裔儿童的血清尿酸浓度与SLC2A9基因变异：Viva La Familia研究
Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.
作者信息
Voruganti V Saroja, Laston Sandra, Haack Karin, Mehta Nitesh R, Cole Shelley A, Butte Nancy F, Comuzzie Anthony G
机构信息
From the Department of Nutrition (VSV) and UNC Nutrition Research Institute (VSV), University of North Carolina at Chapel Hill, Kannapolis, NC; the Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX (SL, KH, SAC, and AGC); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (NRM and NFB).
出版信息
Am J Clin Nutr. 2015 Apr;101(4):725-32. doi: 10.3945/ajcn.114.095364. Epub 2015 Jan 28.
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.
背景
血清尿酸浓度升高与痛风、肾脏疾病和心血管疾病风险增加相关。成人遗传学研究一致发现溶质载体家族2成员9（SLC2A9）基因多态性与血清尿酸水平变化有关。然而，尚不清楚血清尿酸与SLC2A9基因多态性的关联在儿童中是否存在。
目的
旨在研究血清尿酸水平变化是否受遗传影响，以及SLC2A9基因多态性与血清尿酸的关联是否适用于“活力家庭研究”中的西班牙裔儿童。
设计
我们对815名儿童进行了一项包含110万个遗传标记的全基因组关联研究。
结果
我们发现血清尿酸具有显著遗传性[h(2)±标准差=0.45±0.08，P=5.8×10⁻¹¹]，且与SLC2A9变异相关（P值在10⁻¹⁶至10⁻⁷之间）。一些显著相关的多态性先前已在成人研究中得到确认。我们还发现血清尿酸与BMI z评分（ρG=0.45，P=0.002）、体脂百分比（ρG=0.28，P=0.04）、脂肪量（ρG=0.34，P=0.02）、腰围（ρG=0.42，P=0.003）和腰高比（ρG=0.46，P=0.001）之间存在正遗传相关性。
结论
我们的结果表明，西班牙裔儿童血清尿酸水平变化受相当大的遗传影响，并与肥胖相关表型有关。与成人一样，SLC2A9基因变异与西班牙裔儿童血清尿酸浓度相关，血清尿酸是肾脏和心血管疾病风险的重要生物标志物。
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