Advances in studies on the polymorphism of UGT1A1 gene in neonates with unexplained hyperbilirubinemia

Meiling Hu


Neonatal hyperbilirubinemia is a common clinical symptom in the neonatal period. Severe jaundice can cause neonatal bilirubin encephalopathy. Clinically because severe hyperbilirubinemia more causes, the cause of hemolysis and infection is more common, this also accounted for a certain proportion of unknown reasons. UGT1A1 is a key enzyme for bilirubin metabolism, and unexplained jaundice is associated with a decrease in UGT1A1 activity caused by mutations in UGT1A1 gene, leading to neonatal persistent jaundice. The relationship between neonatal unexplained hyperbilirubinemia and UGT1A1 gene polymorphism was reviewed.


UGT1A1 gene polymorphism; Crigler-Najjar syndrome; Gilbert syndrome; neonatal hyperbilirubinemia

Full Text:


Included Database


Shi Hang Ting, Long Jun, Deng Junbiao, et al. Relationship between

UGT1A1 gene polymorphism and neonatal hyperbilirubinemia [J]. Chinese

Journal of Neonatology, 2013,28 (1): 21-24.

Kaplan M, Renbaum P, Levy-Lahad E, et al. Gilbert's asyndrome And

glucose-6-phosphate dehydrogenase deficiency A dose dependent regression

to to neonatal hyperbilirubinemia [J] Proc Natl Acad Sci USA, 1997, 94 (22):


Olusanya B O, Akande A A, Emokpae A, et al. Infants with severe

Neonatal jaundice in Lagos, Nigeria: incidence, correlates And hearing

programs outcomes [J]. Trop Med Int Health, 2009, 14 (3): 310.

Emokpae A A, Mabogunje C A, Imam Z O, et al. Heliotherapy For

neonatal hyperbilirubinemia in southwest, Nigeria: a baseline Pre-

Intervention study [J]. PLoS One, 2016,11 (3): E0151375.

Sgro M, Kandasamy S, Shah V, et al. Severe neonatal hyperbilirubinemia

Decreased after the 2007Canadian guidelines [J]. J Pediatr, 2016, 171: 43-47.

Wang Jin. Investigation of etiology and related genes of neonatal

hyperbilirubinemia [D]. Shanghai: Fudan University, 2011.

Horsfall LJ, Hardy R, Wong A, et al. Genetic variation Common

hereditary hyperbilirubinaemia (Gilbert 's syndrome) And respiratory health

in the 1946British birth cohort [J]. J Hepatol, 2014, 61 (6): 1344- 1351.

Lee J H, Moon K R. Coexistence of gilbert syndrome and hereditary

Spherocytosis in a child presenting with extreme jaundice [J]. Pediatr

Gastroenterol Hepatol Nutr, 2014, 17 (4): 266-269.

Zheng B, Hu G, Yu J, et al. Crigler-Najjar syndrome type II in a Chinese

boy resulting from three mutations in the bilirubin uridine 5'-Diphosphateglucuronosyltransferase

(UGT1A1) gene And a family genetic analysis [J

BMC Pediatr, 2014, 14: 267.

Fevery J, Blanckaert N, Heirwegh KP, et al. Unconjugated Bilirubin and

an increase proportion of bilirubin monoconjugates In the bile of patients

with Gilbert's syndrome and Crigler-Najjar disease [J]. J Clin Invest, 1977, 60

(5): 970-979.

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.

Chaubal A N, Patel R, Choksi D, et al. Management of pregnancy In

Crigler Najjar syndrome type 2 [J]. World J Hepatol, 2016, 8 (11): 530-532.

Clarke DJ, Cassidy AJ, See CG, et al. Cloning of the human UGT1gene

complex in yeast artificial chromosomes: novel Factor of gene structure and

subchromosomal mapping to 2q37 [J] Biochem Soc Trans, 1997, 25 (4):


Farheen S, Sengupta S, Santra A, et al. Gilbert 's syndrome: High

frequency of the (TA) 7TAA allele in India and its interaction With a novel

CAT insertion in promoter of the gene for bilirubin UDPglucuronosyltransferase

gene [J]. World J Gastroenterol, 2006, 12 (14):


Guo Dong, Pang Liangfang, Zhou Honghao. Advances in gene

polymorphism of uridine diphosphate glucuronide transferase gene [J].

Advances in Physiological Sciences, 2010,41 (2): 107-111.

aja O, Tiljak MK, tefanovi M, et al. Correlation UGT1A1TATA-box

polymorphism and jaundice in breastfed Newborns-early presentation of

Gilbert 's syndrome [J]. J Matern Fetal Neonatal Med, 2014, 27 (8 ): 844-850.

Zhou Y, Wang S N, Li H, et al. Association of UGT1A1variants And

hyperbilirubinemia in breast-fed full-term Chinese Infants [J]. PLoS One,

, 9 (8): e104251)

Ma L, Lu H. Relationship between acute cerebral infarction and

hyperhomocysteinemia in young adults [J]. Chinese Journal of Practical

Neurology, 2012,15 (1): 36-37.

Akaba K, Kimura T, Sasaki A, et al. Neonatal hyperbilirubinemia And a

common mutation of the bilirubin uridine diphosphate-

Glucuronosyltransferase gene in Japanese [J]. J Hum Genet, 1999, 44 (1): 22-

Prachukthum S, Nunnarumit P, Pienvichit P, et al. Genetic

Polymorphisms in Thai neonates with hyperbilirubinemia [J]. Acta Paediatr,

, 98 (7): 1106-1110.

Muslu N, Dogruer Z N, Eskandari G, et al. Are glutathione Stransferase

Gene polymorphisms linked to neonatal jaundice [J]. Eur J Pediatr, 2008, 167

(1): 57-61.

Huang C S, Chang P F, Huang M J, et al. Relationship between Bilirubin

UDP-glucuronosyl transferase 1A1gene and Neonatal hyperbilirubinemia [J].

Pediatr Res, 2002, 52 (4): 601-605.

Zhong Dani, Liu Yi, Lin Weixiong. Effect of bilirubin-uridine

diphosphate glucuronosyltransferase gene mutation type on neonatal

hyperbilirubinemia in Guangxi [J]. Journal of Guangxi Medical University,

,25 (6): 838-830.

Long J, Zhang S, Fang X, et al. Association of neonatal

hyperbilirubinemia With uridine diphosphate-glucuronosyltransferase

A1gene polymorphisms: meta-analysis [J]. Pediatr Int, 2011, 53 (4): 530-

Tiwari P K, Bhutada A, Agarwal R, et al. UGT1A1gene variants and

clinical risk factors modulate hyperbilirubinemia in newborns [J]. J Perinatol,

, 34 (2): 120-124.

Ko J S, Chang J Y, Moon J S, et al. Molecular analysis of the UGT1A1

gene in korean patients with Crigler-Najjar syndrome Type II [J]. Pediatr

Gastroenterol Hepatol Nutr, 2014, 17 (1): 37-40.

Wanlapakorn N, Nilyanimit P, Vorawandthanachai T, et al. A Novel stop

codon mutation in exon 1 (558C>A) of the UGT1A1gene in a Thai neonate

with Crigler-Najjar syndrome Type I [J] Genet Mol Res, 2015, 14 (1): 419-

Yamamoto K, Sato H, Fujiyama Y, et al. Contribution of two Missense

mutations (G71Rand Y486D) of the bilirubin UDP Glycosyltransferase

(UGT1A1) gene to phenotypes of Gilbert 'Syndrome and Crigler-Najjar

syndrome type Ⅱ [J] . Biochim Biophys Acta, 1998, 1406 (3): 267-273.

Shibuya A, Itoh T, Tukey R H, et al. Impact of fatty acids on Human

UDP-glucuronosyltransferase 1A1 activity and its expression In neonatal

hyperbilirubinemia [J]. Sci Rep, 2013, 3: 2903.

Aoshima N, Fujie Y, Itoh T, et al. Glucose super buried human UDPglucuronosyltransferase

(UGT) 1A1 to prevent neonatal hyperbilirubinemia

[J]. Sci Rep, 2014, 4: 6343.

Yang H, Wang Q, Zheng L, et al. Multiple genetic modifiers of bilirubin

metabolism involvement in significant neonatal hyperbilirubinemia in

patients of Chinese descent [J]. PLoS One, 2015, 10 (7): e0132034.

Maruo Y, Morioka Y, Fujito H, et al. Bilirubin uridine diphosphate-

Glucuronosyltransferase variation is a genetic basis of Breast milk jaundice

[J]. J Pediatr, 2014, 165 (1): 36-41.

Zhou Y, Wang S N, Li H, et al. Association of UGT1A1variants And

hyperbilirubinemia in breast-fed full-term Chinese Infants [J]. PLoS One,

, 9 (8): e104251.

Deng Chunhong, Xiao Zhaoxia, Wu Zhonghuan. Neonatal

hyperbilirubinemia G6PD deficiency screening and clinical significance [J].

Chinese Journal of Epidemiology and Genetics, 2011,19 (9): 97.

Yang H, Wang Q, Zheng L, et al. Clinical significance of

UGT1A1genetic analysis in Chinese neonates with severe hyperbilirubinemia

[J]. Pediatr Neonatol, 2016, 57 (4): 310-317.

Fu Wenping, Liu Yi. Effect of UGT1A1TATA mutation on G6PD

deficiency neonatal hyperbilirubinemia [J]. Journal of Guangxi Medical

University, 2008,25 (2): 262-263.

Zahedpasha Y, Ahmadpour M, Niaki H, et al relations between neonatal

Icter and Gilbert syndrome in gloucose-6-phosphate dehydrogenase deficient

subjects [J]. J Clin Diagn Res, 2014, 8 (3): 63-65.

Minucci A, Canu G, Concolino P, et al. DNA from buccal swab Is

suitable for rapid genotyping of angiotensin-converting enzyme Insertion /

deletion (I / D) polymorphism [J]. Clin Chim Acta, 2014, 431: 125-130.

Fesenko EE, Heydarov RN, Stepanova EV, et al. Microarray With LNAprobe

for genotyping of polymorphic variants of Gilbert 's syndrome gene

UGT1A1 (TA) n [J]. Clin Chem Lab Med, 2013, 51 (6 ): 1177-1184.

Capper R L, Jin Y K, Lundgren P B, et al. Quantitative high resolution

melting: two methods to determine SNP allele frequencies from pooled

samples [J]. BMC Genet, 2015, 16: 62.

Xu Yuzhong, Chen Qunrong, Sun Shunchang, et al. Analysis of

promoter region A (TA) nTAA polymorphism of UGT1A1 gene by real -

time fluorescence quantitative polymerase chain reaction [J]. International

Journal of Laboratory Medicine, 2016,37 (13): 1806-1808.

DOI: http://dx.doi.org/10.18282/i-cm.v3i1.166

DOI (PDF): http://dx.doi.org/10.18282/i-cm.v3i1.166.g154


  • There are currently no refbacks.