Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI.
Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI.
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DOI：
10.2337/dc08-0349
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发表时间：
2008-08
期刊：
影响因子：
16.2
通讯作者：
Kronenberg F
中科院分区：
文献类型：
--
作者：
Brandstätter A;Kiechl S;Kollerits B;Hunt SC;Heid IM;Coassin S;Willeit J;Adams TD;Illig T;Hopkins PN;Kronenberg F
痛风-高血清尿酸水平导致痛风，并已报告与高血压，肥胖，代谢综合征，2型糖尿病和心血管疾病的风险增加有关。最近，据报道，假定的果糖转运蛋白SLC2A9影响尿酸水平。本研究的目的是检查该基因内的四个单核苷酸多态性与尿酸水平的关联，并确定这种关联是否被肥胖所改变。研究设计和方法--在基于人群的前瞻性Bruneck研究（n = 800）和来自犹他州的病例对照研究中，对SLC2A9内的四个单核苷酸多态性（rs6855911、rs7442295、rs6449213和rs12510549）进行基因分型，该研究包括招募的1,038名重度肥胖受试者和831名对照受试者。结果-我们观察到所有研究组中所有四种多态性与尿酸水平之间存在高度显着相关性。每个拷贝的次要等位基因使年龄和性别调整的尿酸水平平均降低0.30 - 0.35 mg/dl，这意味着相对降低5 - 6%，在联合分析中P值范围为10 − 9至10 − 11。对BMI、肌酸酐、痛风药物和酒精摄入量进行扩展调整后，P值改善至10 - 14至10 - 20范围。这种关联在女性和基于人群的Bruneck研究中更为明显，并受到BMI的显著影响，高BMI个体的效应量更大。结论：SLC2A9内的遗传变异对尿酸水平有显著影响，并受性别和BMI的影响。
OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity. RESEARCH DESIGN AND METHODS—Four single nucleotide polymorphisms within SLC2A9 (rs6855911, rs7442295, rs6449213, and rs12510549) were genotyped in the population-based prospective Bruneck Study (n = 800) and in a case-control study from Utah including 1,038 subjects recruited for severe obesity and 831 control subjects. RESULTS—We observed highly significant associations between all four polymorphisms and uric acid levels in all study groups. Each copy of the minor allele decreased age- and sex-adjusted uric acid levels by 0.30–0.35 mg/dl on average, which translates to a relative decrease of 5–6% with P values ranging from 10−9 to 10−11 in the combined analysis. An extended adjustment for BMI, creatinine, gout medication, and alcohol intake improved P values to a range of 10−14 to 10−20. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI, with stronger effect sizes in individuals with high BMI. CONCLUSIONS—Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and BMI.
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DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
9.8
作者：
Yang, Q;Guo, CY;Fox, CS
通讯作者：
Fox, CS
影响因子：
37.8
作者：
Ford, Earl S.;Li, Chaoyang;Choi, Hyon K.
通讯作者：
Choi, Hyon K.
影响因子：
105.7
作者：
Choi, Hyon K.;Curhan, Gary
通讯作者：
Curhan, Gary
影响因子：
30.8
作者：
Doering, Angela;Gieger, Christian;Meisinger, Christa
通讯作者：
Meisinger, Christa