Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Eur J Med Genet. 2024 Oct;71:104962. doi: 10.1016/j.ejmg.2024.104962. Epub 2024 Jul 26.
The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A (TA)TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)TAA, homozygous p.G71R, compound heterozygous A (TA)TAA/p.G71R and A (TA)TAA/p.P364L, and combined heterozygous A (TA)TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)TAA/p.G71R, single heterozygous A (TA)TAA, single heterozygous p.G71R, and homozygous A (TA)TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.
UDP-葡萄糖醛酸基转移酶 (UGT1A1) 变体的谱，与 Gilbert 综合征 (GS) 和 Crigler-Najjar 综合征 (CNS-II) 相关，在中国和西方国家都有报道。然而，GS 和 CNS-II 中个体 UGT1A1 变体的基因型-表型相关性仍有待阐明。为了探讨 UGT1A1 变体模式和基因型-表型相关性，我们招募了 310 名中国患者，包括 232 名 GS 患者和 78 名 CNS-II 患者。采集外周血样，通过聚合酶链反应和 Sanger 测序筛选 UGT1A1 基因中的变体。分析不同 UGT1A1 变体与临床表型的相关性。共鉴定出 21 种 UGT1A1 变体，包括 9 种新变体，构成 GS 和 CNS-II 患者的 42 种 UGT1A1 基因型。最常见的 UGT1A1 变体是 A (TA)TAA、p.G71R、p.Y486D、p.P364L 和 p.P229Q，与西方国家不同。CNS-II 中 p.Y486D 变体的次要等位基因频率高于 GS，而 GS 中 A (TA)TAA 变体的次要等位基因频率高于 CNS-II。在 UGT1A1 的 14 种重复基因型中，血清总胆红素和甘油三酯有显著差异，其中纯合 p.Y486D (homozygous)/p.G71R 变体的患者血清总胆红素明显高于纯合 A (TA)TAA、纯合 p.G71R、复合杂合 A (TA)TAA/p.G71R 和 A (TA)TAA/p.P364L，以及杂合 A (TA)TAA/p.G71R/p.P229Q，而同时携带 A (TA)TAA (homozygous)/p.P229Q 变体的患者血清甘油三酯明显高于复合杂合 A (TA)TAA/p.G71R、单杂合 A (TA)TAA、单杂合 p.G71R 和纯合 A (TA)TAA。中国患者的 UGT1A1 基因型谱与西方国家明显不同。UGT1A1 重复基因型患者的血清总胆红素和甘油三酯水平存在差异。
