Xiong Q F, Lu Y J, Zou L, Zhou H, Ren H, Feng X N, Yang Y F
Department of Liver Disease, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine; The Clinical Infectious Disease Center of Nanjing, Nanjing 210003, China.
Zhonghua Gan Zang Bing Za Zhi. 2024 Apr 20;32(4):340-345. doi: 10.3760/cma.j.cn501113-20230830-00081.
To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using (2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using -test. 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (=0.652, =0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (=10) and TA7/TA7 (=14) mutations were statistically significant in TBil (=2.143, =0.043). The c.211G>A (p.G71R) heterozygous (=9) and isolated (=15) mutation had no statistical significance in TBil (=0.382, =0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (=270.992, <0.001). There was no statistically significant difference ((2)=3.317, =0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.
分析UGT1A1突变基因（包括增强子、启动子及外显子1 - 5）的分布特征，进一步探讨遗传性非结合胆红素血症患者UGT1A1基因型与临床表型之间的相关性。回顾性分析2015年6月至2022年12月在南京医科大学第二附属医院确诊为遗传性非结合胆红素血症的患者。对所有患者采用桑格测序法检测UGT1A1基因。进行全血细胞计数、肝功能及腹部影像学检查。分类变量数据采用（2）检验或费舍尔精确检验进行比较。正态分布的连续变量数据采用 -检验进行比较。112例（男∶女比例为81∶31，年龄9 - 70岁）患有遗传性非结合胆红素血症，共鉴定出14个突变位点，其中7个为确诊突变，频率由高到低依次为：（TA）n占50%，c.211G>A（p.G71R）占49.10%，1456T>G（p.Y486D）占16.96%，c.686C>A（p.R229W）占12.5%，1091C>T（p.P364L）占8.04%，c - 3279T>G占0.982%。同时，所有患者有1至4个突变，其中仅1个突变最为常见（55.36%），其次为2个突变（37.5%），罕见的3个和4个突变（分别为5.36%和1.78%）。四组间总胆红素（TBil）水平差异无统计学意义（=0.652，=0.583）。1个突变在（TA）n和c.211G>A（p.G71R）中最为常见，其中TA6/TA7（=10）和TA7/TA7（=14）突变在TBil方面差异有统计学意义（=2.143，=0.043）。c.211G>A（p.G71R）杂合（=9）及纯合（=15）突变在TBil方面差异无统计学意义（=0.382，=0.706）。GS组占75%，中间组占16.9%，CNS -Ⅱ组占8%。三组间TBil差异有统计学意义（=270.992，<0.001）。GS组、中间组及CNS -Ⅱ组中，突变1（分别为44例、14例和4例）与突变≥2（分别为40例、5例和5例）之间差异无统计学意义（（2）=3.317，=0.19）。遗传性非结合胆红素血症患者中，UGT1A1基因突变位点数量可能对TBil水平无协同作用。TA7/TA7突变并不少见，且TBil水平相对较高。
