Dataset Information

Common variants in the SLC28A2 gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese.

ABSTRACT: Background:Serum uric acid (SUA), hyperuricemia (HUA) and gout are complex traits with relatively high heritability. This study aims to identify whether a candidate gene, SLC28A2, exerts susceptibility for SUA fluctuation and incidence of HUA and gout in the Han Chinese population. Results:Three sample sets of 1376 gout patients, 1290 long-term HUA subjects (no gout attack) and 1349 normouricemic controls were recruited for this study. Eight polymorphisms in the SLC28A2 gene were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. Rs16941238 showed the most significant associations with SUA level (minor allele "A", BETA?=?-?13.84??mol/L, P?=?0.0041, Pperm?=?0.0042) and HUA (OR?=?0.7734, P?=?0.0033, Pperm?=?0.0020), but not with gout (OR?=?0.8801, P?=?0.1315, Pperm?=?0.1491). Rs2271437 was significantly associated with gout (minor allele "G", OR?=?1.387, P?=?0.0277, Pperm?=?0.0288), and was further confirmed in the meta-analysis with the previously published gout GWAS dataset (OR?=?1.3221, P?=?0.0089). Each variant basically conferred consistent OR direction on gout and HUA, compared with the normouricemic control. Conclusions:Our findings support the associations of the SLC28A2 gene with the SUA level, the HUA phenotype and gout in Han Chinese.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC6335706 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Common variants in the <i>SLC28A2</i> gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese.

Zhou Zhaowei Z Li Zhiqiang Z Wang Can C Li Xinde X Cheng Xiaoyu X Li Changgui C Shi Yongyong Y

Hereditas 20190116

<h4>Background</h4>Serum uric acid (SUA), hyperuricemia (HUA) and gout are complex traits with relatively high heritability. This study aims to identify whether a candidate gene, <i>SLC28A2</i>, exerts susceptibility for SUA fluctuation and incidence of HUA and gout in the Han Chinese population.<h4>Results</h4>Three sample sets of 1376 gout patients, 1290 long-term HUA subjects (no gout attack) and 1349 normouricemic controls were recruited for this study. Eight polymorphisms in the <i>SLC28A2< ...[more]

PMID: 30679935

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Project description:Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited.A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort.Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females.Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.

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Dataset Information

Common variants in the SLC28A2 gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese.

Publications

Common variants in the <i>SLC28A2</i> gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese.

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