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

abstract: ...Background Gout 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 casecontrol association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese. Methods A 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. Results No deviation from the HardyWeinberg 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). Conclusions Three 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.

...BMC Med Genet BMC Med. Genet BMC Medical Genetics 1471-2350 BioMed Central London 26290326 4593200 208 10.1186/s12881-015-0208-8 Research Article Polymorphisms in GCKR , SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a casecontrol study Zhou Zhao-Wei zhouzhaoweiqd@hotmail.com Cui Ling-Ling cuillqd@163.com Han Lin hanlinqd@126.com Wang Can wangcanabc@126.com Song Zhi-Jian zhijiansong@126.com Shen Jia-Wei celaoforever@hotmail.com Li Zhi-Qiang lizqsjtu@163.com Chen

..., rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis. Results No deviation from the HardyWeinberg 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). Conclusions Three 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. Keywords Gout SNPs GCKR SLC17A1 SLC22A12 issue-copyright-statement The Author(s) 2015 Background Gout is the most common cause of arthritis and elevated serum uric acid (SUA) level, namely hyperuricemia, is an important independent risk factor for gout [ 1 ]. There are extensive data which suggests that the incidence and prevalence of hyperuricemia and gout increased markedly over the past decades worldwide [ 2 5 ]. In addition, hyperuricemia and gout have been independently linked to other endocrine and metabolic diseases

... , SLC17A1-SLC17A3 and the newly identified genes PDZK1 , GCKR , LRRC16A , SLC16A9 and SLC22A11 [ 17 ]. Another large-scale GWAS from >140,000 individuals of European ancestry for SUA level also replicated most of these nine significant loci and additional 18 new loci [ 18 ]. A study of Netherland residents corroborated the association of PDZK1 , GCKR , SLC16A9 and SLC22A11 loci with altered SUA concentrations, but failed to replicate the LRRC16A locus as a risk factor [ 19 ]. A study of Germans

... rs1183201 in SLC17A1 was also corroborated to be associated with gout in New Zealand Caucasians [ 24 , 25 ] and rs1165205 in SLC17A3 (in high linkage disequilibrium (LD) with rs1183201 in HapMap-CEU, r 2 =0.889) was replicated in European whites [ 8 ]. Noticeably, a recent GWAS in Chinese population identified two previously reported SUA loci of SLC2A9 (rs11722228) and ABCG2 (rs2231142, rs4148152 and rs3114018, rs4148155), but failed to replicate the remaining loci which were associated with SUA level

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Gene: SLC17A1 - solute carrier family 17 (organic anion transporter), member 1 - (NCBI)

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