A urate gene-by-diuretic interaction and gout risk in participants with hypertension

Results from the ARIC study

Mara Ann McAdams Demarco, Janet W. Maynard, Alan Baer, Linda W. Kao, Anna Kottgen, Josef Coresh

Research output: Contribution to journalArticle

Abstract

Objective: To test for a urate gene-by-diuretic interaction on incident gout. Methods: The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results: Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions: Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

Original languageEnglish (US)
Pages (from-to)701-706
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume72
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Gout
Uric Acid
Diuretics
Genes
Hypertension
Sodium Potassium Chloride Symporter Inhibitors
Sodium Chloride Symporter Inhibitors
Single Nucleotide Polymorphism
Incidence
Genetic Predisposition to Disease
Polymorphism
Anions
Logistics
Atherosclerosis
Nucleotides
Logistic Models
Genotype
Kidney
Population

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

A urate gene-by-diuretic interaction and gout risk in participants with hypertension : Results from the ARIC study. / McAdams Demarco, Mara Ann; Maynard, Janet W.; Baer, Alan; Kao, Linda W.; Kottgen, Anna; Coresh, Josef.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 5, 05.2013, p. 701-706.

Research output: Contribution to journalArticle

@article{cd5c5b2ec0824439b586d2b3c5ced036,
title = "A urate gene-by-diuretic interaction and gout risk in participants with hypertension: Results from the ARIC study",
abstract = "Objective: To test for a urate gene-by-diuretic interaction on incident gout. Methods: The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results: Of 3524 participants with hypertension, 33{\%} used a diuretic and 3.1{\%} developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3{\%}). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95{\%} CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95{\%} CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions: Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.",
author = "{McAdams Demarco}, {Mara Ann} and Maynard, {Janet W.} and Alan Baer and Kao, {Linda W.} and Anna Kottgen and Josef Coresh",
year = "2013",
month = "5",
doi = "10.1136/annrheumdis-2011-201186",
language = "English (US)",
volume = "72",
pages = "701--706",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "5",

}

TY - JOUR

T1 - A urate gene-by-diuretic interaction and gout risk in participants with hypertension

T2 - Results from the ARIC study

AU - McAdams Demarco, Mara Ann

AU - Maynard, Janet W.

AU - Baer, Alan

AU - Kao, Linda W.

AU - Kottgen, Anna

AU - Coresh, Josef

PY - 2013/5

Y1 - 2013/5

N2 - Objective: To test for a urate gene-by-diuretic interaction on incident gout. Methods: The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results: Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions: Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

AB - Objective: To test for a urate gene-by-diuretic interaction on incident gout. Methods: The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results: Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions: Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

UR - http://www.scopus.com/inward/record.url?scp=84875915261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875915261&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2011-201186

DO - 10.1136/annrheumdis-2011-201186

M3 - Article

VL - 72

SP - 701

EP - 706

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 5

ER -