GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10362220" target="_blank" >RIV/00216208:11110/17:10362220 - isvavai.cz</a>

Alternative codes found

RIV/00023728:_____/17:N0000045

Result on the web

<a href="http://dx.doi.org/10.1136/annrheumdis-2016-209632" target="_blank" >http://dx.doi.org/10.1136/annrheumdis-2016-209632</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/annrheumdis-2016-209632" target="_blank" >10.1136/annrheumdis-2016-209632</a>

Result language

angličtina

Original language name

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

Original language description

Objective: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. Results: In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p&lt;5.0x10-8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (pmeta=3.58x10-8). Conclusions: Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30226 - Rheumatology

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Annals of the Rheumatic Diseases

ISSN

0003-4967

e-ISSN

—

Volume of the periodical

76

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

869-877

UT code for WoS article

000398387200015

EID of the result in the Scopus database

2-s2.0-85006010711