Chiddarwar Ashish S, D'Silva Selma Z, Colah Roshan B, Ghosh Kanjaksha, Mukherjee Malay B
National Institute of Immunohaematology (ICMR), 13th Floor, NMS Building, K.E.M Hospital Campus, Parel, Mumbai, 400012, India.
Department of Haematogenetics, National Institute of Immunohaematology (ICMR), 13th Floor, NMS Building, K.E.M Hospital Campus, Parel, Mumbai, 400012, India.
Mol Biol Rep. 2018 Dec;45(6):2733-2739. doi: 10.1007/s11033-018-4305-6. Epub 2018 Aug 13.
The present study was undertaken to investigate genetic variations present in the coding regions of the UGT1A1 gene among the Gilbert's syndrome patients. Analysis of genetic variations was performed by direct DNA sequencing among the patients that do not have any polymorphic variations in the promoter regions of the UGT1A1 gene. We identified seven different sequence variations among Gilbert's Syndrome patients, of which four were novel. Out of seven variants, six missense and one silent single nucleotide substitutions were present in the UGT1A1 gene. In addition, molecular modeling of UGT1A1 (H55R, P152S and N212H) variants suggested a reduced activity of the enzyme. This study demonstrates that different variations present in the UGT1A1 gene and specifically, the H55R variation had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.
本研究旨在调查吉尔伯特综合征患者中UGT1A1基因编码区存在的基因变异。对UGT1A1基因启动子区域无任何多态性变异的患者进行直接DNA测序，以分析基因变异。我们在吉尔伯特综合征患者中鉴定出七种不同的序列变异，其中四种是新发现的。在这七个变异中，UGT1A1基因存在六个错义单核苷酸替换和一个沉默单核苷酸替换。此外，UGT1A1（H55R、P152S和N212H）变异的分子建模表明该酶活性降低。本研究表明，UGT1A1基因中存在的不同变异，特别是H55R变异对胆红素水平有显著影响，可能是高胆红素血症的遗传危险因素。
