Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets
Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets
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病例对照样本组中 CLNK 基因和 ZNF518B 基因的遗传变异与痛风相关
DOI：
10.1007/s00296-015-3215-3
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发表时间：
2015-07-01
影响因子：
4
通讯作者：
Kang, Longli
中科院分区：
文献类型：
--
作者：
Jin, Tian-bo;Ren, Yongchao;Kang, Longli
一项对欧洲人群痛风的全基因组关联研究发现了12个与痛风风险密切相关的遗传变异，但尚不清楚这些变异是否也与中国人群的痛风风险有关。共有145名痛风患者和310名健康对照患者参加了病例对照关联研究。对12个CLNK和ZNF518B基因的SNPs进行基因分型，并进行关联分析。用具有95%可信区间(CI)的优势比(OR)来评估这种关联。总体而言，我们发现了4个痛风的危险等位基因：CLNK基因中rs2041215和rs1686947的等位基因“G”(OR1.66；95%CI1.04-2.63；p=0.031)(OR2.19；95%CI1.38-3.46；p=0.001)和加性模型(OR1.39；95%CI1.00-1.93；p=0.049)(OR1.67；95%CI1.19-2.32；隐性模型分析ZNF518B基因rs10938799和rs10016022的等位基因“A”(OR4.66；95%CI1.44~15.09；p=0.008)(OR4.54；95%CI1.23~16.76；p=0.020)。进一步的单倍型分析显示，痛风患者中CLNK的TCATTCTGA单倍型频率更高(调整后OR0.48；95%CI0.24~0.95；p=0.036)。此外，rs2041215、rs10938799和rs17467273基因多态性也与临床病理参数相关。本研究提供了痛风易感基因CLNK和ZNF518B在中国人群中存在的证据，它们可能成为痛风患者的诊断和预后标志物。
A genome-wide association study of gout in European populations identified 12 genetic variants strongly associated with risk of gout, but it is unknown whether these variants are also associated with gout risk in Chinese populations. A total of 145 patients with gout and 310 healthy control patients were recruited for a case-control association study. Twelve SNPs of CLNK and ZNF518B gene were genotyped, and association analysis was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the association. Overall, we found four risk alleles for gout in patients: the allele "G" of rs2041215 and rs1686947 in the CLNK gene by dominant model (OR 1.66; 95 % CI 1.04-2.63; p = 0.031) (OR 2.19; 95 % CI 1.38-3.46; p = 0.001) and additive model (OR 1.39; 95 % CI 1.00-1.93; p = 0.049) (OR 1.67; 95 % CI 1.19-2.32; p = 0.003), respectively, and the allele "A" of rs10938799 and rs10016022 in ZNF518B gene by recessive model (OR 4.66; 95 % CI 1.44-15.09; p = 0.008) (OR 4.54; 95 % CI 1.23-16.76; p = 0.020). Further haplotype analysis showed that the TCATTCTGA haplotype of CLNK was more frequent among patients with gout (adjusted OR 0.48; 95 % CI 0.24-0.95; p = 0.036). Additionally, polymorphisms of rs2041215, rs10938799, and rs17467273 were also correlated with clinical pathological parameters. This study provides evidence for gout susceptibility genes, CLNK and ZNF518B, in a Chinese population, which may have potential as diagnostic and prognostic marker for gout patients.