Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; Physical Examination Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Gene. 2021 May 20;781:145526. doi: 10.1016/j.gene.2021.145526. Epub 2021 Feb 23.
Gilbert's syndrome (GS) is a mild condition characterized by periods of hyperbilirubinemia, which results in variations in the UDP-glucuronosyltransferase 1 (UGT1A1) gene. Variant genotypes of UGT1A1 vary in different populations in the world. The present study aimed to determine the genotype of the UGT1A1 promoter and exon that are related to the serum total bilirubin (STB) level in the Chinese Han population. A total of 120 individuals diagnosed with GS (GS group) and 120 healthy individuals (non-GS group) were enrolled. Routine blood, liver function tests, and antibodies associated with autoimmune liver diseases were assessed. Blood samples were collected for DNA purification. Sequencing of the UGT1A1 promoter and exons was conducted for post segment amplification by PCR. Compound heterozygous UGT1A128 and UGT1A16 (25/120, 20.83%), single homozygous UGT1A128 (24/120, 20.00%) and single heterozygous UGT1A16 (18/120, 15.00%) were the most frequent genotypes in the GS group. However, single heterozygous UGT1A16 (30/120, 25.00%) and single heterozygous UGT1A128 (19/120, 15.83%) were the most frequent genotypes in the non-GS group. Further, the frequencies of single homozygous UGT1A128, compound heterozygous UGT1A128 and UGT1A16, and compound heterozygous UGT1A128, UGT1A16 and UGT1A127 were significantly higher in the GS group than those in the non-GS group. The STB levels of GS patients with the homozygous UGT1A128 genotype were remarkably higher than those of patients with other genotypes. Homozygous UGT1A128 and heterozygous UGT1A16 variants were associated with the highest and lowest risks of hyperbilirubinemia, respectively. Our study revealed that compound heterozygous UGT1A128 and UGT1A16, or single homozygous UGT1A128 are major genotypes associated with GS in Chinese Han people. These findings might facilitate the precise genomic diagnosis of Gilbert's syndrome.
吉尔伯特综合征（GS）是一种轻度病症，其特征为周期性高胆红素血症，导致尿苷二磷酸葡萄糖醛酸转移酶 1（UGT1A1）基因变异。UGT1A1 的变异基因型在世界不同人群中存在差异。本研究旨在确定与中国汉族人群血清总胆红素（STB）水平相关的 UGT1A1 启动子和外显子的基因型。共纳入 120 例诊断为 GS（GS 组）和 120 例健康个体（非 GS 组）。评估常规血液、肝功能检查和与自身免疫性肝病相关的抗体。采集血液样本进行 DNA 纯化。通过 PCR 进行后片段扩增对 UGT1A1 启动子和外显子进行测序。在 GS 组中，最常见的基因型为复合杂合 UGT1A128 和 UGT1A16（25/120，20.83%）、纯合子 UGT1A128（24/120，20.00%）和单杂合子 UGT1A16（18/120，15.00%）。然而，在非 GS 组中，最常见的基因型为单杂合子 UGT1A16（30/120，25.00%）和单杂合子 UGT1A128（19/120，15.83%）。此外，GS 组中纯合子 UGT1A128、复合杂合 UGT1A128 和 UGT1A16 以及复合杂合 UGT1A128、UGT1A16 和 UGT1A127 的频率显著高于非 GS 组。UGT1A128 纯合基因型 GS 患者的 STB 水平明显高于其他基因型患者。纯合子 UGT1A128 和杂合子 UGT1A16 变体分别与高胆红素血症的最高和最低风险相关。本研究表明，复合杂合 UGT1A128 和 UGT1A16 或纯合子 UGT1A128 是与中国汉族人 GS 相关的主要基因型。这些发现可能有助于吉尔伯特综合征的精确基因组诊断。
