Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Kidney Int. 2012 Mar;81(5):502-7. doi: 10.1038/ki.2011.414. Epub 2011 Dec 21.
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.
尿酸血清水平升高与高血压密切相关，但两者之间的关联方向仍存在争议。为了明确这种关系，我们在一个同质的阿米什社区内采用了对照环境，并对 SLC2A9 基因中的一个非同义编码单核苷酸多态性 rs16890979（Val253lle）进行了孟德尔随机化分析。该基因表达的 GLUT9 转运蛋白也可转运尿酸，与血清尿酸水平降低有关。我们研究了 516 名阿米什成年人在标准化饮食条件下的基因型与血压之间的无偏关联，每位参与者连续 6 天都接受高盐和低盐饮食，中间有洗脱期。在这两种饮食期间，使用 24 小时动态血压监测来测量血压，作为主要结局。所有参与者均未服用利尿剂或其他降压药物，评估了 GLUT9 基因型与血清尿酸和血压之间的关系。发现每个 GLUT9 次要 Ile 等位基因都使血清尿酸降低 0.44mg/dl，分别与高盐和低盐饮食下收缩压平均降低 2.2 和 1.5mmHg 显著相关。因此，使用 GLUT9 基因中的变异进行的孟德尔随机化分析表明，血清尿酸降低可通过因果关系降低血压。
