Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia
Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evalua...
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Elsevier
2020-10-01
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| Series: | Pediatrics and Neonatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957220300887 |
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| author | May-Jen Huang Yu-Cheng Lin Kevin Liu Pi-Feng Chang Ching-Shan Huang |
| author_facet | May-Jen Huang Yu-Cheng Lin Kevin Liu Pi-Feng Chang Ching-Shan Huang |
| author_sort | May-Jen Huang |
| collection | DOAJ |
| description | Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p < 0.001). Only the AOR of those carrying UGT1A1 activity ranked 31–40% of normal was statistically significant (AOR = 3.16, p < 0.001). For the hyperbilirubinemic neonates exclusively breastfed, AOR for the development of hyperbilirubinemia is positively correlated to degree of variation (AOR = 1.95, 2.19 and 4.53; with p = 0.003, 0.05 and < 0.001, respectively), while the effect of UGT1A1 enzyme activity was varied (AOR = 1.02–3.72, with p = 0.95∼<0.001). Conclusion: The estimated enzyme activity depending on combination of SNPs (genotypes) in the UGT1A1 gene could not be utilized to explain the development of neonatal hyperbilirubinemia. We reconfirm that the −53 A(TA)7TAA/A(TA)7TAA is not, while the 211AA is a risk factor for the development of neonatal hyperbilirubinemia in Taiwanese. |
| format | Article |
| id | doaj-art-00865e6b27384266a67fca1a40d86544 |
| institution | OA Journals |
| issn | 1875-9572 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
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| series | Pediatrics and Neonatology |
| spelling | doaj-art-00865e6b27384266a67fca1a40d865442025-08-20T02:01:46ZengElsevierPediatrics and Neonatology1875-95722020-10-0161550651210.1016/j.pedneo.2020.05.009Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemiaMay-Jen Huang0Yu-Cheng Lin1Kevin Liu2Pi-Feng Chang3Ching-Shan Huang4Department of Clinical Pathology, Cathay General Hospital, Taipei, TaiwanDepartment of Pediatrics, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei City, Taiwan; Department of Electronic Engineering, Oriental Institute of Technology, Pan-Chiao, New Taipei City, TaiwanDepartment of Pediatrics, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei City, TaiwanDepartment of Pediatrics, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei City, Taiwan; Department of Electronic Engineering, Oriental Institute of Technology, Pan-Chiao, New Taipei City, Taiwan; Corresponding author. Department of Pediatrics, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S. Rd, Pan-Chiao, New Taipei City, 220, Taiwan.Department of Clinical Pathology, Cathay General Hospital, Taipei, Taiwan; Corresponding author. Department of Clinical Pathology, Cathay General Hospital, No. 280, Sec. 4, Ren Ai Rd, Taipei, 106, Taiwan.Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p < 0.001). Only the AOR of those carrying UGT1A1 activity ranked 31–40% of normal was statistically significant (AOR = 3.16, p < 0.001). For the hyperbilirubinemic neonates exclusively breastfed, AOR for the development of hyperbilirubinemia is positively correlated to degree of variation (AOR = 1.95, 2.19 and 4.53; with p = 0.003, 0.05 and < 0.001, respectively), while the effect of UGT1A1 enzyme activity was varied (AOR = 1.02–3.72, with p = 0.95∼<0.001). Conclusion: The estimated enzyme activity depending on combination of SNPs (genotypes) in the UGT1A1 gene could not be utilized to explain the development of neonatal hyperbilirubinemia. We reconfirm that the −53 A(TA)7TAA/A(TA)7TAA is not, while the 211AA is a risk factor for the development of neonatal hyperbilirubinemia in Taiwanese.http://www.sciencedirect.com/science/article/pii/S1875957220300887enzyme activityneonatal hyperbilirubinemiasingle nucleotide polymorphismUGT1A1variation status |
| spellingShingle | May-Jen Huang Yu-Cheng Lin Kevin Liu Pi-Feng Chang Ching-Shan Huang Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia Pediatrics and Neonatology enzyme activity neonatal hyperbilirubinemia single nucleotide polymorphism UGT1A1 variation status |
| title | Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia |
| title_full | Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia |
| title_fullStr | Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia |
| title_full_unstemmed | Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia |
| title_short | Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia |
| title_sort | effects of variation status and enzyme activity for udp glucuronosyltransferase 1a1 gene on neonatal hyperbilirubinemia |
| topic | enzyme activity neonatal hyperbilirubinemia single nucleotide polymorphism UGT1A1 variation status |
| url | http://www.sciencedirect.com/science/article/pii/S1875957220300887 |
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