Current address: Department of Core Technology, R&D Center, LG Household & Healthcare (LG H&H), Seoul, 07795, South Korea.
Department of Life Science, Sogang University, Seoul, 04107, Republic of Korea.
BMC Med Genet. 2020 Dec 17;21(1):241. doi: 10.1186/s12881-020-01177-w.
Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.
A total of 10 CFB genetic polymorphisms were selected and genotyped in 1716 study subjects comprised of 955 CHB patients and 761 population controls.
A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91 × 10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS.
rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.
乙型肝炎可引起多种形式的肝脏疾病，包括慢性乙型肝炎（CHB）和肝细胞癌。先前对 CHB 风险的全基因组关联研究表明，补体因子 B（CFB）的 rs12614 与 CHB 风险显著相关。在这项研究中，对先前报道的 GWAS 单核苷酸多态性（SNP；CFB rs12614）进行了精细映射研究，以验证 rs12614 对 CHB 易感性的遗传效应，并确定 rs12614 周围可能存在的其他因果变异。进行这项关联研究是为了确定 CFB 单核苷酸多态性（SNPs）的遗传效应，并确定韩国人群中 CHB 易感的额外独立因果标记。
选择了总共 10 个 CFB 遗传多态性，并对包括 955 名 CHB 患者和 761 名人群对照在内的 1716 名研究对象进行了基因分型。
CFB 外显子 2 中的非同义变异 rs12614（Arg32Trp）与 CHB 风险显著相关（比值比=0.43，P=5.91×10）。进一步的连锁不平衡和条件分析证实，rs12614 与先前鉴定的 CHB 标记物具有独立的遗传效应，对 CHB 易感性有影响。计算了遗传风险评分（GRS），CHB 患者的 GRS 高于人群对照。此外，发现随着累积 GRS 的增加，OR 显著增加。
rs12614 在韩国人群中对 CHB 风险有显著的遗传影响。因此，rs12614 可能被用作 CHB 易感性的潜在因果遗传变异。
