Clinical Characteristics and Polymorphism of UGT1A1 Gene in 53 Cases of Congenital Hyperbilirubinemia in Yunnan

Juan LI; Chengjun DENG; Shuli HE; Ying LI; Meifen WANG

Article Contents

Article Navigation > Journal of Kunming Medical University > 2024 >

Juan LI, Chengjun DENG, Shuli HE, Ying LI, Meifen WANG. Clinical Characteristics and Polymorphism of UGT1A1 Gene in 53 Cases of Congenital Hyperbilirubinemia in Yunnan[J]. Journal of Kunming Medical University.

Citation:

Juan LI, Chengjun DENG, Shuli HE, Ying LI, Meifen WANG. Clinical Characteristics and Polymorphism of UGT1A1 Gene in 53 Cases of Congenital Hyperbilirubinemia in Yunnan[J]. Journal of Kunming Medical University.

Citation:

PDF( 622 KB)

Clinical Characteristics and Polymorphism of UGT1A1 Gene in 53 Cases of Congenital Hyperbilirubinemia in Yunnan

1.
Dept. of Gastroenterology
2.
Dept. of Infection，Kunming Children’s Hospital，Kunming Yunnan 650034，China

Received Date: 2023-11-01
Available Online: 2024-04-29

Abstract

Abstract

Objective To investigate the clinical characteristics of 53 cases of congenital hyperbilirubinemia （Gilbert syndrome, Crigler-Najjar syndrome） caused by UGT1A1 gene mutation in Yunnan Province and the characteristics of UGT1A1 gene mutation. Methods 53 cases were selected from the Department of Gastroenterology of Kunming Children's Hospital from January 2017 to December 2022 and divided into Gilbert syndrome （GS） group and Crigler-Najjar-2 （GN-2）group. The clinical data and genetic test results of children with type I1 syndrome （CN-2 group）and the clinical manifestations, laboratory test results and gene polymorphisms of the children were retrospectively analyzed. Results Children from the ethnic minority had the higher incidence in both groups. The proportion of females in CN-2 group was higher than that in GS group. In terms of liver system, the levels of TBil and IDB in CN-2 group were higher than those in GS group, with statistical significance （all P values < 0.05）. The liver structure in GS group was normal, while 3 patients in CN-2 group had the abnormal liver and biliary structure. In the extra-hepatic system, there were no abnormalities in blood system and glucose metabolism, abnormal blood lipids and thyroid function metabolism, vitamin D deficiency in GS group, vitamin A and D deficiency and vitamin E decreased in CN-2group. There were cardiac structural abnormalities in both groups, but the incidence of CN-2 group was higher than that of GS group. Among all the patients, the mutation frequency of c.1456T>G in exon 5 was the highest （32 cases, 60.37%）, followed by c.1091C>T （14 cases, 60.37%）. Exon 1, C.211g>A （6 cases, 11.32%）, and C.1198a >C （4 cases, 7.55%）. The frequency of c.1456T>G mutation in GS group and CN-2 group was 69.23% and 57.5%（9 and 23 cases）, respectively, and there was no significant difference between the two groups （P > 0.05）. Among the two groups, the second most frequent mutation was c.1091C>T （4 cases and 10 cases）, and there was no statistical significance between the two groups （P > 0.05）.The frequencies of UGT1A1 haplotypes 1、3 and 4 were statistically significant between GS group and CN-2 group （P < 0.05）. There is no significant difference in gender and ethnic groups among the four major mutation forms of UGT1A1 （P > 0.05）. Conclusion The clinical manifestations of the liver system and extrahepatic system are different between GS group and CN-2 group. The highest mutation frequency of UGT 1A1 gene is c.1456T>G （32 cases, 60.37%） in exon 5.
- Gilbert syndrome,
- Crigler-Najjar syndrome,
- Serum total bilirubin,
- Uridine diphosphate glucuronuronic transferase 1A1,
- Genotype

FullText(HTML)

References(13)

References

[1]	Sun L,Li M,Zhang L,et al. Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II[J]. Medicine (Baltimore),2017,96(45):e8620.
[2]	Canu G,Minucci A,Zuppi C,et al. Gilbert and Crigler Najjar syndromes: An update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database[J]. Blood Cells Mol Dis,2013,50(4):273-280. doi: 10.1016/j.bcmd.2013.01.003
[3]	Li L,Deng G,Tang Y,et al. Spectrum of UGT1A1 variations in Chinese patients with Crigler-Najjar syndrome type II[J]. PLoS One,2015,10(5):e0126263. doi: 10.1371/journal.pone.0126263
[4]	Chen H L,Wu S H,Hsu S H,et al. Recent advances in the diagnosis and treatment of inherited cholestatic liver diseases[J]. J Biomed Sci,2018,25(1):75. doi: 10.1186/s12929-018-0475-8
[5]	Ivanov A,Semenova E. Bilirubin level and UGT1A1 28 genotype in men of north-west region of Russia[J]. J Clin Exp Hepatol,2021,11(6):691-699. doi: 10.1016/j.jceh.2021.01.006
[6]	Trabelsi N,Chaouch L,Haddad F,et al. Novel mutations in Uridyl-diphosphate-glucuronosyl-transferase 1A1 (UGT1A1) gene in Tunisian patients with unconjugated hyperbilirubinemia[J]. Eur J Med Genet,2021,64(2):104-139.
[7]	Shiu T Y,Huang H H,Lin H H,et al. Restriction fragment length polymorphism effectively identifies exon 1 mutation of UGT1A1 gene in patients with Gilbert's Syndrome[J]. Liver Int,2015,35(8):2050-2056. doi: 10.1111/liv.12785
[8]	Maruo Y,Nakahara S,Yanagi T,et al. Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome[J]. J Gastroenterol Hepatol,2016,31(2):403-408. doi: 10.1111/jgh.13071
[9]	Li Y,Qu Y J,Zhong X M,et al. Two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene[J]. J Zhejiang Univ Sci B,2014,15(5):474-481. doi: 10.1631/jzus.B1300233
[10]	Xiong Q F,Zhong Y D,Feng X N,et al. Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia[J]. Zhonghua Gan Zang Bing Za Zhi,2018,26(12):898-902.
[11]	Abuduxikuer K,Fang L J,Li L T,et al. UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children[J]. Medicine (Baltimore),2018,97(49):e13576.
[12]	Sampietro M,Lolascon A. Molecular pathology of Crigler-Najjar type I and II and Gilbert's syndromes[J]. Haematologica,1999,84(2):150-157.
[13]	陈伟,林美丽,王玉,等. UGT1A1基因多态性与新生儿不明原因非结合性高胆红素血症相关性研究[J]. 中华新生儿科杂志,2019,34(2):81-86.

Relative Articles(20)

Relative Articles

[1]	Lianyong CHEN, Xing YANG, Haohao RU, Tao CHEN, Shuangqun YAN, Lin XU. Analysis of Molecular Characteristics of Mycobacterium Tuberculosis and Factors Associated with Transmission in Yunnan Province. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230821
[2]	Yuying ZHANG, Zhijun ZENG, Huichao CHEN, Xiaobin ZHANG, Zhaojun YANG, Jie DAI, Lijuan DONG, Wanyue ZHANG, Yanling MA, Min CHEN. Analysis of Chlamydia Trachomatis Genotype among Female Sex Workers in Yunnan Province. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230224
[3]	Xiaomei JIN, Jieyan HE, Jichang SHI, Hui XING, Hong WANG, Ju ZHANG, Lijuan DONG, Lihua HUANG, Min CHEN, Zhijuan CHEN, Huichao CHEN. Virus Genotypes and Drug Resistance among HIV/AIDS Patients before Antiretroviral Therapy in Dali Bai Autonomous Prefecture in 2018. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20231123
[4]	Jianping HE, Mengxin LV, Maohua QIN, Lihong ZHU, Fengbo DANG, Yongbo SUN, Shengjun LUO, Lan LUO, Jian TANG. Gene Variation Analysis of 357 Cases with Gilbert Syndrome in Kunming. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20231015
[5]	Xiaowei YUAN, Maohua QIN, Lijun WANG, Yuanqi DUAN. Expression of CRP，IL-6 and TNF-a in Serum of Patients with Adolescence Polycystic Ovary Syndrome. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20221026
[6]	Jin-yun CAI, Juan WANG, Rui-xi SUN, Ping FU. Clinical Features of Rhupus Syndrome. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20210201
[7]	Le Xiao Jing , Chen Jie , Zhang Fan , Li Hui Fang . . Journal of Kunming Medical University,
[8]	Jiang Yu Hui , Liu Ling , He Can Lin , Li Yang . . Journal of Kunming Medical University,
[9]	Zhou Yong Ming , Li Wen Liang . The Progress in the Clinical Research of Lynch Syndrome. Journal of Kunming Medical University,
[10]	Deng De Yao , Yuan Wen Li , Wu Guang Juan , Chen Di , Li Li Li , Gao Zong Ying , Liu Chang , Gu Jin Yi . Analysis of the Carbapenemase Genotype in the Carbapenem-resistant Acinetobacter Baumannii in Traumatology Department. Journal of Kunming Medical University,
[11]	Cui Kun Hua , Li Qi . Vitamin D Receptor Gene TaqI Polymorphisms and Steroid Responsiveness in Childhood Nephrotic Syndrome. Journal of Kunming Medical University,
[12]	Zhang Le , Tang Li Bin , Jiang Jian Jie , Xia Jia Wei , Lv Zheng Xuan , Li Yun Zhen , Han Liu Xin , Bai Bin . Non Biological Artificial Liver Technology in Treatment of Liver Failure and Hepatorenal Syndrom. Journal of Kunming Medical University,
[13]	Yang Bi Qing , Wang Xun . Significance of Serum Total Bilirubin Level in Cerebral Emergencies. Journal of Kunming Medical University,
[14]	Wang Wen Li . . Journal of Kunming Medical University,
[15]	Wang Chao Qun . . Journal of Kunming Medical University,
[16]	Deng De Yao . . Journal of Kunming Medical University,
[17]	Tang Jin Ling . . Journal of Kunming Medical University,
[18]	Yan Xiao Hong . . Journal of Kunming Medical University,
[19]	Liu Ling . . Journal of Kunming Medical University,
[20]	Liu De Sheng . . Journal of Kunming Medical University,