title: Genotype-based changes in serum uric acid affect blood pressure.
abstract: 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.
authors.affiliation: Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. aparsa@medicine.maryland.edu
authors.forename: Afshin
authors.initials: A
authors.lastname: Parsa
authors.forename: Eric
authors.initials: E
authors.lastname: Brown
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Fink
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D061365:Amish / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004039:Diet, Sodium-Restricted; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000178:diet therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014527:Uric Acid / Q000097:blood*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D017673:Sodium Chloride, Dietary; D014527:Uric Acid