Genetic polymorphisms in bilirubin metabolism genes and their association with unconjugated Hyperbilirubinemia among adults.
The present study was undertaken to investigate the genotype and allele frequencies of the variants in the bilirubin metabolism genes (UGT1A1, OATP2, HMOX1 and BLVRA) and their association with hyperbilirubinemia in adults. Genotyping of fifteen genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. 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 62% of the cases showed the presence of more than 4 variants as compared to 20% of the controls and the mean total serum bilirubin levels also increased according to the number of variants co-expressed. Exon-wise sequencing of the UGT1A1 gene revealed a variant at nt 6846 A àG in exon 2, with a predicted amino acid change of Ile à Val at codon 322 in heterozygous condition among the hyperbilirubinia cases. Hence, this study demonstrates that polymorphisms in the bilirubin metabolism genes have a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.