Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case–control study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08-20

AUTHORS

Zhao-Wei Zhou, Ling-Ling Cui, Lin Han, Can Wang, Zhi-Jian Song, Jia-Wei Shen, Zhi-Qiang Li, Jian-Hua Chen, Zu-Jia Wen, Xiao-Min Wang, Yong-Yong Shi, Chang-Gui Li

ABSTRACT

BackgroundGout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case–control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese.MethodsA total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis.ResultsNo deviation from the Hardy–Weinberg equilibrium was observed either in the case or control cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p = 1.78E−4, OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E−7, OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p = 3.94E−5; rs1183201 in SLC17A1, corrected p = 0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with rs780094 (located in GCKR, corrected p = 2.96E−4). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p = 0.143).ConclusionsThree SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future. More... »

PAGES

66

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12881-015-0208-8

    DOI

    http://dx.doi.org/10.1186/s12881-015-0208-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043330532

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26290326


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        "description": "BackgroundGout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case\u2013control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese.MethodsA total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis.ResultsNo deviation from the Hardy\u2013Weinberg equilibrium was observed either in the case or control cohorts (corrected p\u2009>\u20090.05). Three SNPs, rs780094 (located in GCKR, corrected p\u2009=\u20091.78E\u22124, OR\u2009=\u20090.723), rs1183201 (located in SLC17A1, corrected p\u2009=\u20091.39E\u22127, OR\u2009=\u20090.572) and rs505802 (located in SLC22A12, corrected p\u2009=\u20090.007, OR\u2009=\u20090.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p\u2009=\u20093.94E\u22125; rs1183201 in SLC17A1, corrected p\u2009=\u20090.005; rs505802 in SLC22A12, corrected p\u2009=\u20090.003) and of triglycerides with rs780094 (located in GCKR, corrected p\u2009=\u20092.96E\u22124). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p\u2009=\u20090.402; rs780094 vs rs505802, p\u2009=\u20090.434; rs1183201 vs rs505802, p\u2009=\u20090.143).ConclusionsThree SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.", 
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