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Genetic Variations in Bilirubin Metabolism Genes and Their Association with Unconjugated Hyperbilirubinemia in Adults
Author(s) -
Chiddarwar Ashish S.,
D'Silva Selma Z.,
Colah Roshan B.,
Ghosh Kanjaksha,
Mukherjee Malay B.
Publication year - 2017
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12179
Subject(s) - genotyping , biology , bilirubin , genotype , genetics , gene , glucuronosyltransferase , allele , genetic association , single nucleotide polymorphism , endocrinology , microsome , in vitro
Summary Objective : The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes ( UGT1A1, OATP2, HMOX1 , and BLVRA ) and their association with hyperbilirubinemia. Material and Methods : Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR‐RFLP, GeneScan analysis, and direct DNA sequencing. Results : Genetic polymorphisms of the UGT1A1 promoter, specifically the T‐3279G phenobarbital‐responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1 , and BLVRA genes, were significantly higher among the cases than the controls. Further, nearly 82% of the cases showed the presence of significantly four or more variants as compared to 37% of the controls ( P < 0.0001) and the mean total serum bilirubin levels also increased according to the number of variants co‐expressed. Conclusions : This study demonstrates that polymorphisms in the bilirubin metabolism genes had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.