UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates.@*METHODS@#A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced.@*RESULTS@#In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05).@*CONCLUSIONS@#UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.

Prevalence of UGT1A1 (TA)n promoter polymorphism in Panamanians neonates with G6PD deficiency

A relationship between the polymorphism in promoter region of the UGT1A1 gene and the development of jaundice has been demonstrated recently. This polymorphism leads to 30% of normal rate transcription initiation of UGT1A1 gene, thus decreasing the bilirubin glucuronidation. The combination of the G6PD deficiency and polymorphism in neonates and adults may cause pronounced hyperbilirubinaemias. The aim of this study was to analyse the variations in the UGT1A1 gene promoter in Panamanians neonates with G6PD deficiency and its association with neonatal jaundice (NJ). We identified five different genotypes of TA repeats, in 17 neonates (42.5%) the normal variant TA6/TA6 and in the other 57.5% of the subjects: TA7/TA7 (12.5%), TA6/TA7 (40%), TA6/ TA8 (2.5%) and TA6/TA5 (2.5%). Additionally 75% of the 16 newborns that showed NJ had an abnormal variant in the promoter sequence, although, there was no significant difference (P = 0.068). The risk of jaundice in neonates with TA7 variant was thrice higher in subjects than with other alleles (P = 0.093, CI: 0.81–11.67). The TA7 allele frequency in this study (0.325) was consistent with the global frequency and similar to Caucasians. The results proved that there is no significant relationship between promoter polymorphism in UGT1A1 and NJ in G6PD deficient Panamanian newborns. Further studies with a greater number of subjects would determine the exact relationship between marked NJ and UGT1A promoter variations.

Meta-analysis of Association between Irinotecan-induced 3-4 Degree Neutropenia and UGT1A1 Gene Poly-morphism / 中国药房

OBJECTIVE:To evaluate the association between UGT1A1 gene polymorphism and irinotecan-induced 3-4 degree neutropenia,and to provide evidenced-based reference for clinical treatment. METHODS:Retrieved from CJFD,Wanfang data-base,VIP,PubMed,EMBase,Science direct and Cochrane library,related studies about UGT1A1*28 and UGT1A1*6 gene polymorphism and irinotecan-induced 3-4 degree neutropenia were collected. After data extraction and quality evaluation of included studies,Meta-analysis was conducted by using Review Man 5.3 software. RESULTS:A total of 29 studies were included,involv-ing 2408 patients. UGT1A1*28 includ wild genotype TA 6/6(UGT1A1*1/*1)and mutations genotype TA 6/7(UGT1A1*1/*28)、TA 7/7(UGT1A1*28/*28),UGT1A1*6 includ wild genotype GG and mutations genotype GA、AA. Results of Meta-analysis showed:the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=1.92,95%CI(1.52,2.44),P<0.001;UGT1A1*6:OR=2.49, 95%CI(1.46,4.26),P<0.001]. Using medium-dose and high-dose of irinotecan,the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P<0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P<0.001]. Using low-dose of irinotecan,there was no statistical significance in the incidence of 3-4 degree neutropenia between UGT1A1*28,UGT1A1*6 mutations genotype and wild genotype [UGT1A1*28:OR=1.20,95%CI(0.70,2.08),P=0.51;UGT1A1*6:OR=3.19,95%CI (0.85,11.89),P=0.08]. CONCLUSIONS:Using medium-dose and high-dose of irinotecan,UGT1A1*28 and UGT1A1*6 muta-tions will increase the risk of severe neutropenia in cancer patients. Using low-dose of irinotecan,there is no clear correlation be-tween gene polymorphism and the neutropenia.

Analysis on A(TA)n TAA polymorphism of UGT1A1 gene promoter by fluorescence real-time quantitative PCR / 国际检验医学杂志

Objective To develop a new method to detect A (TA)n TAA polymorphism in the UGT1A1 gene promoter by fluo‐rescence real‐time quantitative PCR (RQ‐PCR) .Methods Genomic DNA was extracted from peripheral blood in 16 patients with Gilbert′s syndrome and 66 healthy individuals .The polymorphic A(TA)n TAA sequence in the UGT1A1 gene promoter was deter‐mined by DNA sequencing .A pair of primers and two TaqMan probes labeled with either 5′FAM or VIC reporter dye incorporated a 3′minor groove binder were designed .The A(TA)n TAA polymorphisms in the UGT1A1 gene promoter were identified by RQ‐PCR for all research subjects .The sensitivity and specificity of RQ‐PCR for detecting the A(TA)nTAA polymorphisms were veri‐fied by DNA sequencing method .Results The homozygous A(TA)7TAA polymorphism was found in the promoter region of the UGT1A1 gene in all 16 patients with Gilbert′s syndrome by using RQ‐PCR .The homozygous A(TA)6TAA polymorphism was foundin46healthysubjects,whiletheheterozygousA(TA)6TAA/A(TA)7TAApolymorphismwasfoundinother20healthysub‐jects .All A(TA)nTAA polymorphisms in the promoter region of the UGT1A1 gene identified by RQ‐PCR were consistent with that of DNA sequencing .Conclusion It is a sensitive ,specific and simple method to detect the A (TA)n TAA polymorphisms in the promoter region of the UGT1A1 gene by RQ‐PCR ,which can be promoted and applied in clinic .

Analysis on Gene Polymorphism of UGT1A1 Gene Promoter in Patients with Malignant Tumour / 现代检验医学杂志

Objective To detect UGT1A1 gene promoter polymorphism with gene sequence method and analyze the distribu-tion of UGT1A1*28 and UGT1A1*6 gene polymorphism in Wuhan.Methods A total of 230 samples were collected from tumor patient in Medical Oncology Department of Renmin Hospital of Wuhan University from January 2013 to December 2014,then gene sequence of the target fragments were detected by Sanger sequencing method and analyzed patient UGT1A1 gene promoter polymorphism TA box.Results In this research examination 230 example tumor patient,198 patients (86.1%)were identified with TA6/TA6 genotype,29 patients (12.6%)were identified with TA6/TA7 genotype,3 pa-tients (1.3%)TA7/TA7 variant.Conclusion TA6/TA6 wild-typewas higher frequence in patients with malignant tumour in Wuhan.

UDP-glucuronosyltransferase 1A1 Gene Polymorphism in Severe Neonatal Hyperbilirubinemia

PURPOSE: TATA box mutation/polymorphism in the promoter region of the bilirubin uridinediphosphoglucuronate glucuronosyltransferase 1A1 (UGT-1A1) gene is known to be an etiology of hyperbilirubinemia. This study examined if a TATA box mutation/polymorphism in UGT-1A1 gene promoter could be associated with the development of severe early neonatal jaundice in Korean infants. METHODS: Thirty-nine neonatal jaundice patients and 40 controlled infants were analyzed for UGT-1A1 promoter genotypes by using DNA sequencing. RESULTS: The homozygote for (TA)7TAA mutation was not found in this study. Comparison of the prevalence of UGT-1A1 promoter (TA)7TAA heterozygotes revealed no difference between the group with jaundice and the controlled group (15.4% vs. 10%). The peak bilirubin level was higher and the onset of jaundice was earlier in the jaundice group with (TA)7TAA heterozygote compared to the jaundice group without (TA)7TAA heterozygote (23.2+/-1.0 mg/dL vs. 19.7+/-2.4 mg/dL, P=0.004, 5.0+/-1.5 days vs. 8.3+/-4.1 days, P= 0.057). CONCLUSION: The results of this study showed that TATA box polymorphism in UGT-1A1 gene promoter did not increase the prevalence of severe early neonatal jaundice in Korean infants.