Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population
Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population
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DOI：
10.1111/liv.12740
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发表时间：
2015-08-01
影响因子：
6.7
通讯作者：
Kim, Yoon-Jun
中科院分区：
文献类型：
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作者：
Cheong, Hyun Sub;Lee, Jeong-Hoon;Kim, Yoon-Jun
背景和目标：B型肝炎病毒（HBV）感染是慢性B型肝炎（CH B）、肝硬化和肝细胞癌的最严重危险因素。最近，几项全基因组关联研究（GWAS）确定了与亚洲人群CHB风险相关的重要变异。具体来说，我们之前的GWAS将VARS 2-SFTA 2基因区域鉴定为CHB的遗传风险位点之一。研究方法：为了进一步描述这种关联并分离其中可能的因果变异，我们通过对VARS 2和SFTA 2基因附近的更多SNP进行基因分型进行了额外的关联研究。总共分析了3902名受试者（1046例病例和2856例对照）中VARS 2-SFTA 2的14个SNP。结果如下：Logistic回归分析显示，包括先前报道的rs 2532932在内的6个SNPs与CHB的风险显著相关（P = 1.7 x 10（-10），类似于0.002）。进一步的连锁不平衡和条件分析确定了两个变异（rs 9394021和rs 2517459）作为CHB遗传危险因素的新标记，而不是我们以前研究报告的SNP（rs 2532932）。为了评估基于所有已知遗传因素的CHB累积风险，计算遗传风险评分（GRS）。正如预期的那样，根据GRS，病例组与对照组的风险等位基因数量分布明显不同。同样，比值比（OR）增加（OR = 0.32-3.97）。结论：我们的研究结果表明，VARS 2-SFTA 2基因区域的常见变异与韩国人群中的CHB显著相关，这可能有助于进一步了解CHB的遗传易感性。
Background & Aims: Hepatitis B virus (HBV) infection is the most serious risk factor for chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) identified important variants associated with the risk of CHB in Asian populations. Specifically, our previous GWAS identified the VARS2-SFTA2 gene region as one of the genetic risk loci for CHB. Methods: To further characterize this association and to isolate possible causal variants within it, we performed an additional association study by genotyping more SNPs in the vicinity of the VARS2 and SFTA2 genes. In all, 14 SNPs of VARS2-SFTA2 were analysed among a total of 3902 subjects (1046 cases and 2856 controls). Results: Logistic regression analysis revealed that six SNPs, including the previously reported rs2532932, were significantly associated with the risk of CHB (P = 1.7 x 10(-10)similar to 0.002). Further linkage disequilibrium and conditional analysis identified two variants (rs9394021 and rs2517459) as new markers of genetic risk factors for CHB rather than the reported SNP from our previous study (rs2532932). To evaluate the cumulative risk for CHB based on all known genetic factors, genetic risk score (GRS) were calculated. As anticipated, the distribution of the number of risk alleles in cases vs. controls clearly differed according to the GRS. Similarly, the odds ratios (ORs) were increased (OR = 0.32-3.97). Conclusion: Our findings show that common variants in the VARS2-SFTA2 gene region are significantly associated with CHB in a Korean population, which may be useful in further understanding genetic susceptibility to CHB.