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Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome.
Kaohsiung J Med Sci. 2019 Jul; 35(7):432-439.KJ

Abstract

Variations at the six nucleotides -3279 (T > G), -53 (A[TA]6 TAA > A[TA]7 TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P < .001 for each). Among the 178 patients of Gilbert's syndrome, serum bilirubin value was inversely correlated with UGT1A1 activity (r = -.306, P < .001). The sensitivity was 72.0% and the specificity was 90.5% by using UGT1A1 activity ≦40% of normal as the cut-off point to distinguish between healthy subjects and patients of Gilbert's syndrome. Our results demonstrate that UGT1A1 activity is certainly a determinate for serum bilirubin value and UGT1A1 activity ≦40% of normal is a proper risk factor for the development of Gilbert's syndrome.

Authors+Show Affiliations

Department of Clinical Pathology, Cathay General Hospital, Taipei, Taiwan.Department of Internal Medicine, Changhua Christian Medical Foundation Changhua Christian Hospital, Changhua, Taiwan.Department of Clinical Pathology, Cathay General Hospital, Taipei, Taiwan.Liver Unit, Cathay General Hospital, Taipei, Taiwan.Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.Department of Clinical Pathology, Cathay General Hospital, Taipei, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31017737

Citation

Huang, May-Jen, et al. "Effect of UDP-glucuronosyltransferase 1A1 Activity On Risk for Developing Gilbert's Syndrome." The Kaohsiung Journal of Medical Sciences, vol. 35, no. 7, 2019, pp. 432-439.
Huang MJ, Chen YC, Huang YY, et al. Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome. Kaohsiung J Med Sci. 2019;35(7):432-439.
Huang, M. J., Chen, Y. C., Huang, Y. Y., Yang, S. S., Chen, P. L., & Huang, C. S. (2019). Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome. The Kaohsiung Journal of Medical Sciences, 35(7), 432-439. https://doi.org/10.1002/kjm2.12077
Huang MJ, et al. Effect of UDP-glucuronosyltransferase 1A1 Activity On Risk for Developing Gilbert's Syndrome. Kaohsiung J Med Sci. 2019;35(7):432-439. PubMed PMID: 31017737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome. AU - Huang,May-Jen, AU - Chen,Yi-Chun, AU - Huang,Yang-Yang, AU - Yang,Sien-Sing, AU - Chen,Pei-Lain, AU - Huang,Ching-Shan, Y1 - 2019/04/24/ PY - 2019/02/16/received PY - 2019/04/08/accepted PY - 2019/4/25/pubmed PY - 2020/2/7/medline PY - 2019/4/25/entrez KW - Gilbert's syndrome KW - UDP-glucuronosyltransferase 1A1 KW - bilirubin KW - genotypes SP - 432 EP - 439 JF - The Kaohsiung journal of medical sciences JO - Kaohsiung J. Med. Sci. VL - 35 IS - 7 N2 - Variations at the six nucleotides -3279 (T > G), -53 (A[TA]6 TAA > A[TA]7 TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P < .001 for each). Among the 178 patients of Gilbert's syndrome, serum bilirubin value was inversely correlated with UGT1A1 activity (r = -.306, P < .001). The sensitivity was 72.0% and the specificity was 90.5% by using UGT1A1 activity ≦40% of normal as the cut-off point to distinguish between healthy subjects and patients of Gilbert's syndrome. Our results demonstrate that UGT1A1 activity is certainly a determinate for serum bilirubin value and UGT1A1 activity ≦40% of normal is a proper risk factor for the development of Gilbert's syndrome. SN - 2410-8650 UR - https://www.unboundmedicine.com/medline/citation/31017737/Effect_of_UDP_glucuronosyltransferase_1A1_activity_on_risk_for_developing_Gilbert's_syndrome_ L2 - https://doi.org/10.1002/kjm2.12077 DB - PRIME DP - Unbound Medicine ER -