Department of Internal Medicine, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Korea.
DNALink, Inc., Seoul, Korea.
PLoS One. 2020 Feb 21;15(2):e0229374. doi: 10.1371/journal.pone.0229374. eCollection 2020.
Although genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population.
We performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants.
A total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10-8 and 5.61×10-8, respectively [discovery set]; P = 4.08×10-15 and 9.92×10-16, respectively [validation set]). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10-15 and 1.26×10-15, respectively [discovery set]; P = 4.13×10-10 and 5.15×10-11, respectively [validation set]). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10-64 and 2.05×10-62, respectively [discovery set]; P = 1.33×10-116 and 2.24×10-118, respectively [validation set]). No genome-wide significant associations was found for ALT.
We demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity.
尽管不同种族之间存在遗传特征差异，但很少有全基因组关联研究（GWAS）报道过影响肝酶表达的遗传决定因素。本研究旨在评估全基因组单核苷酸多态性（SNP）与韩国人群肝酶之间的关联。
我们进行了 GWAS，以鉴定影响肝功能的遗传基因座，肝功能通过碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）、γ-谷氨酰转移酶（GGT）和总胆红素（BIL）的浓度来衡量。
共纳入 6488 名受试者（发现队列 4457 名，验证队列 2031 名）。受试者的平均年龄为 50.0±10.6 岁（男性 53.7%）。在测试的 546738 个 SNP 中，rs651007 和 rs579459 位于 ABO 基因中，与 ALP 呈强相关（发现集分别为 P = 1.63×10-8 和 5.61×10-8；验证集分别为 P = 4.08×10-15 和 9.92×10-16）。此外，位于 GGT1 基因中的 rs5751901 和 rs2006092 与 GGT 呈强相关（发现集分别为 P = 6.44×10-15 和 1.26×10-15；验证集分别为 P = 4.13×10-10 和 5.15×10-11）。在与总胆红素水平具有全基因组显著意义的 13 个 SNP 中，rs10929302 和 rs6742078 显示出最显著的关联（发现集分别为 P = 3.08×10-64 和 2.05×10-62；验证集分别为 P = 1.33×10-116 和 2.24×10-118）。ALT 与全基因组无显著关联。
我们证明了 ABO、GGT1 和 UGT1A 家族分别与韩国人群的 ALP、GGT 和 BIL 相关。这些发现与欧洲人群 GWAS 报道的结果在相关基因和位置上存在差异，表明根据种族的不同，肝酶调节的遗传机制也不同。
