Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study
Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study
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DOI：
10.3945/ajcn.114.095364
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发表时间：
2015-04-01
影响因子：
7.1
通讯作者：
Comuzzie, Anthony G.
中科院分区：
文献类型：
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作者：
Voruganti, V. Saroja;Laston, Sandra;Comuzzie, Anthony G.
背景：血清尿酸浓度升高与痛风以及肾脏和心血管疾病的风险增加有关。在成人中的遗传学研究一致地发现溶质携带者家族2，成员9(SLC2A9)的多态与血清尿酸的变化有关。目的：探讨血尿酸的变异是否受遗传因素的影响，以及与SLC2A9基因多态性的关联是否适用于家庭万岁的西班牙裔儿童。设计：我们对815名儿童进行了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的遗传性[h(2)+/-sd=0.45+/-0.08，P=5.8×10(-1)1]，与SLC2A9变异体相关(P值在10(-16)至10(-7)之间)。先前在成人研究中发现了几个显著相关的基因多态。血尿酸与BMIz评分(Rho(G)=0.45，P=0.002)、体脂百分比(Rho(G)=0.28，P=0.04)、脂肪质量(Rho(G)=0.34，P=0.02)、腰围(Rho(G)=0.42，P=0.003)、腰高比(PG=0.46，P=0.003)呈正相关。P=0.001)。结论：我们的结果表明西班牙裔儿童的血尿酸变化受到相当大的遗传影响，并与肥胖相关的表型有关。与成年人一样，在西班牙裔儿童中，SLC2A9的基因变异与血尿酸浓度有关，血尿酸浓度是肾脏和心血管疾病风险的重要生物标志物。
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 X 10(-1)1] 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 (rho(G) = 0.45, P = 0.002), percentage of body fat (rho(G) = 0.28, P = 0.04), fat mass (rho(G) = 0.34, P = 0.02), waist circumference (rho(G) = 0.42, P = 0.003), and waist-toheight ratio (PG = 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.