Cheong Hyun Sub, Lee Jeong-Hoon, Yu Su Jong, Yoon Jung-Hwan, Lee Hyo-Suk, Cheong Jae Youn, Cho Sung Won, Park Neung Hwa, Park Byung Lae, Namgoong Suhg, Kim Lyoung Hyo, Shin Hyoung Doo, Kim Yoon-Jun
Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Liver Int. 2015 Aug;35(8):1934-40. doi: 10.1111/liv.12740. Epub 2015 Jan 10.
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.
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).
Logistic regression analysis revealed that six SNPs, including the previously reported rs2532932, were significantly associated with the risk of CHB (P = 1.7 × 10(-10) ~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).
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.
乙型肝炎病毒（HBV）感染是慢性乙型肝炎（CHB）、肝硬化和肝细胞癌最严重的风险因素。最近，几项全基因组关联研究（GWAS）在亚洲人群中确定了与CHB风险相关的重要变异。具体而言，我们之前的GWAS将VARS2 - SFTA2基因区域确定为CHB的遗传风险位点之一。
为了进一步表征这种关联并分离其中可能的因果变异，我们通过对VARS2和SFTA2基因附近更多的单核苷酸多态性（SNP）进行基因分型，开展了一项额外的关联研究。总共对3902名受试者（1046例病例和2856名对照）分析了VARS2 - SFTA2的14个SNP。
逻辑回归分析显示，包括先前报道的rs2532932在内的6个SNP与CHB风险显著相关（P = 1.7×10⁻¹⁰~0.002）。进一步的连锁不平衡和条件分析确定了两个变异（rs9394021和rs2517459）是CHB遗传风险因素的新标记，而非我们之前研究报道的SNP（rs2532932）。为了基于所有已知遗传因素评估CHB的累积风险，计算了遗传风险评分（GRS）。正如预期的那样，根据GRS，病例组与对照组中风险等位基因数量的分布明显不同。同样，优势比（OR）增加（OR = 0.32 - 3.97）。
我们的研究结果表明，VARS2 - SFTA2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。
