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Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion.
J Rheumatol. 2014 Sep; 41(9):1863-70.JR

Abstract

OBJECTIVE

Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors.

METHODS

Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control.

RESULTS

Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion.

CONCLUSION

Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Torres RJ
From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University. rtorres.hulp@salud.madrid.org.
de Miguel E
From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
Bailén R
From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
Banegas JR
From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
Puig JG
From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.

MeSH

AgedAllelesFemaleGoutHumansHyperuricemiaMaleMiddle AgedOrganic Anion TransportersPolymorphism, Single NucleotideUric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25128519

Citation

Torres, Rosa J., et al. "Tubular Urate Transporter Gene Polymorphisms Differentiate Patients With Gout Who Have Normal and Decreased Urinary Uric Acid Excretion." The Journal of Rheumatology, vol. 41, no. 9, 2014, pp. 1863-70.
Torres RJ, de Miguel E, Bailén R, et al. Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. J Rheumatol. 2014;41(9):1863-70.
Torres, R. J., de Miguel, E., Bailén, R., Banegas, J. R., & Puig, J. G. (2014). Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. The Journal of Rheumatology, 41(9), 1863-70. https://doi.org/10.3899/jrheum.140126
Torres RJ, et al. Tubular Urate Transporter Gene Polymorphisms Differentiate Patients With Gout Who Have Normal and Decreased Urinary Uric Acid Excretion. J Rheumatol. 2014;41(9):1863-70. PubMed PMID: 25128519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. AU - Torres,Rosa J, AU - de Miguel,Eugenio, AU - Bailén,Rebeca, AU - Banegas,José R, AU - Puig,Juan G, Y1 - 2014/08/15/ PY - 2014/8/17/entrez PY - 2014/8/17/pubmed PY - 2015/5/26/medline KW - ARTHRITIS KW - GENE POLYMORPHISM KW - GOUT SP - 1863 EP - 70 JF - The Journal of rheumatology JO - J Rheumatol VL - 41 IS - 9 N2 - OBJECTIVE: Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors. METHODS: Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control. RESULTS: Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion. CONCLUSION: Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/25128519/Tubular_urate_transporter_gene_polymorphisms_differentiate_patients_with_gout_who_have_normal_and_decreased_urinary_uric_acid_excretion_ DB - PRIME DP - Unbound Medicine ER -