Association between gout and polymorphisms in GCKR in male Han Chinese

Wang, Jing; Liu, Shiguo; Wang, Binbin; Zhang, Miao; Han, Lin; Chu, Nan; Zhang, Kun; Meng, Dong; Li, Changgui; Ma, Xu

doi:10.1007/s00439-012-1151-9

Cited by 33 publications

(21 citation statements)

References 19 publications

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“…In Chinese population, rs6855911 (in strong LD with rs734553 in HapMap-CHB, r 2 = 1.0) was not identified in gout-control groups but was replicated in high-uric-acid and normal-uric-acid groups [ 26 ] and rs16890979 was in much lower LD with rs734553 from HapMap-CHB (r 2 = 0.494). GCKR rs780093 (in strong LD with rs780094 in HapMap-CEU and HapMap-CHB, r 2 = 1.0) was nominally associated with gout in Europeans and Chinese [ 12 , 23 ]. SLC17A1 rs1165196 (in strong LD with rs1183201 from HapMap-CEU, r 2 = 0.889) was associated with SUA level in whites [ 8 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…The risk alleles of GCKR , SLC16A9 , SLC22A11 and INHBC are associated with an average increase in serum urate of 0.004 mmol/L6. Of these loci, the effect size in gout of GCKR is consistently higher—it is associated with gout in European, Chinese, Japanese and Polynesian sample sets (table 1)6 8 9 with OR=1.3–1.5 in sample sets where gout is clinically ascertained. INHBC is also consistently associated in European and Polynesian with OR=∼1.15, although with a lower effect size than GCKR (table 1).…”

Section: Discussionmentioning

confidence: 99%

Twenty-eight loci that influence serum urate levels: analysis of association with gout

et al. 2014

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“…RFX3 has also been found to be necessary for the differentiation and function of mature beta-cells and regulates GCK expression and mature beta-cell function by binding to its promoter 19 . Interestingly, GCKR, another regulatory protein of GCK, was reported to be associated with serum uric acid levels in individuals of European descent 8 and with gout in the Han Chinese 20 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese

Liu

et al. 2015

Nat Commun

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Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10−13, BCAS3), 9p24.2 (rs12236871, P=1.48 × 10−10, RFX3) and 11p15.5 (rs179785, P=1.28 × 10−8, KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.

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Association between gout and polymorphisms in GCKR in male Han Chinese

Cited by 33 publications

References 19 publications

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

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

Twenty-eight loci that influence serum urate levels: analysis of association with gout

Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese

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