engleski

UGT1A1 gene promoter polymorphism: a new genetic risk factor for autoimmune hepatitis?

Autoimmune hepatitis (AIH) is a rare autoimmune disease of unknown etiology including different environmental and genetic factors. The aim of this study was to evaluate the polymorphism in the promoter region of the UGT1A1 gene (6TA repeats → 7TA repeats) and effect on serum bilirubin in AIH patients. 6 patients (5 female, 1 male) from 4 to 17 yrs with confirmed AIH (5 AIH type I, 1 AIH type II) and total/unconjugated bilirubin ranging from 38.1/22.5 μ mol/L to 162.2/77.7 μ mol/L, admitted to Department of Pediatrics in a period of 2 years, were included in the study. Genomic DNA was extracted from EDTA blood and UGT1A1 6TA→ 7TA polymorphism detected by PCR amplification followed by high-resolution electrophoresis on Spreadex gel. All studied patients were UGT1A1 7 allele carriers, 4 of them were heterozygotes (6/7) and 2 were homozygotes (7/7). Both 7/7 homozygotes were AIH type I, with total/unconjugated bilirubin 57.3/51.0 and 162.2/77.7 μ mol/L, respectively. Four of 6/7 heterozygotes were AIH type I and one AIH type II. Their total/unconjugated bilirubin ranged from 38.1/22.5 to 129.1/66.1 μ mol/L. Some genetic polymorphisms are implicated to favor AIH, such as HLA DR3 allele associated with early onset, HLA DR4 associated with late onset and C4AQ0 allele resulting in lower level of complement C4. According to our results, UGT1A1 7 allele is responsible for unexpectedly high proportion of unconjugated/total bilirubin in AIH patients and impose a possibility to be a new genetic risk factor for AIH associated with early onset.

autoimmune hepatitis; UGT1A1 polymorphism

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