Genotype-based changes in serum uric acid affect blood pressure.
Genotype-based changes in serum uric acid affect blood pressure.
复制标题
DOI：
10.1038/ki.2011.414
复制
发表时间：
2012-03
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
血清尿酸水平升高与高血压相关，但这种相关性的方向性仍有争议。为了帮助定义这种关系，我们在一个同质的阿米什社区内使用了一个受控环境，并在SLC 2A 9基因中使用了非同义编码单核苷酸多态性rs 16890979（Val 253 Ile）的孟德尔随机化。该基因表达GLUT 9转运蛋白，该转运蛋白也转运尿酸，并与较低的血清尿酸水平相关。我们研究了516名阿米什成年人的基因型和血压之间的无混杂关联，每个人都被放置在标准化饮食6天，首先是高钠，其次是低钠，中间有一个洗脱期。血压，采用24小时动态监测，在两个饮食期间被用作主要结果。所有参与者均未使用利尿剂或其他抗高血压药物，并评估了GLUT 9基因型与血清尿酸和血压之间的关系。研究发现，GLUT 9次要Ile等位基因的每个拷贝均可使血清尿酸显着降低0.44 mg/dl，并且与高钠和低钠饮食中收缩压分别显着平均降低2.2和1.5 mm Hg相关。因此，使用GLUT 9基因变体的孟德尔随机化分析表明，血清尿酸的降低具有降低血压的因果效应。
Elevated serum levels of uric acid consistently correlate with hypertension, but the directionality of the association remains debated. To help define this relationship, we used a controlled setting within a homogeneous Amish community and the Mendelian randomization of a nonsynonymous coding single-nucleotide polymorphism, rs16890979 (Val253Ile), in the SLC2A9 gene. This gene expresses the GLUT9 transporter that also transports uric acid and is associated with lower serum uric acid levels. We studied the unconfounded association between genotype and blood pressure in 516 Amish adults, each placed for 6 days on standardized diets, first with high sodium, followed by low sodium, with an intervening washout period. Blood pressure, measured using 24-h ambulatory monitoring, during both diet periods was used as the primary outcome. All participants were free of diuretic or other antihypertensive medications and the relationships between GLUT9 genotype and both serum uric acid and blood pressure were assessed. Each copy of the GLUT9 minor Ile allele was found to confer a significant 0.44 mg/dl reduction in serum uric acid and was associated with a significant mean decrease in the systolic blood pressure of 2.2 and 1.5 mm Hg on the high- and low-sodium diet, respectively. Thus, a Mendelian randomization analysis using variants in the GLUT9 gene indicates that a decrease in serum uric acid has a causal effect of lowering blood pressure.
登录
查看更多内容
影响因子：
19.6
作者：
Khosla, UM;Zharikov, S;Johnson, RJ
通讯作者：
Johnson, RJ
影响因子：
158.5
作者：
CANNON, PJ;STASON, WB;LARAGH, JH
通讯作者：
LARAGH, JH
影响因子：
4.8
作者：
Anzai, Naohiko;Ichida, Kimiyoshi;Sakurai, Hiroyuki
通讯作者：
Sakurai, Hiroyuki
影响因子：
120.7
作者：
Fang, J;Alderman, MH
通讯作者：
Alderman, MH
影响因子：
2.8
作者：
Kato, M;Hisatome, I;Somers, VK
通讯作者：
Somers, VK