Prevalence of 2 UGT1A1 Gene Variations Related to Gilbert’s Syndrome in South of Iran: An Epidemiological, Clinical, and Genetic Study

Background Gilbert’s syndrome can present as a chronic or benign asymptomatic condition, characterized by a slight increase in the serum bilirubin level without any hemolysis. In 1995, a genetic variation, located in the TATA box of UGT1A1 gene promoter, was identified in patients with Gilbert’s syndrome. Also, further analysis identified a new missense variation, Gly71Arg, within the codon region of UGT1A1 gene. Coincidence of TATA box and Gly71Arg variations and their relationship with clinical findings are mostly variable. Objectives The aim of this study was to determine TATA box and Gly71Arg variations of UGT1A1 gene and assess their effects on clinical findings in patients with Gilbertʹs syndrome in southern provinces of Iran. Methods In this cross sectional study, 213 unrelated infants and children, below 12 years, who were admitted to the pediatric ward of Namazi hospital, Shiraz, Iran, were enrolled from June 2015 to May 2016. Blood-extracted DNA was used for genotyping TATA box and Gly71Arg variations by sequencing. Further biochemical analyses were performed for each patient. Results About 78.9% of the studied subjects had normal homozygous genotypes, and 21.1% were heterozygous for the Gly71Arg variation. In total, 34% of the cases were normal in the promoter region (TA6/6), and 55% were heterozygous with genotypes TA6/7, TA6/5, and TA 6/8. Three combinations of genotypes, ie, TA6/7-Gly/Gly, TA7/7-Gly/Gly, and TA7/7-Gly/Arg, showed significant differences in the serum total bilirubin level. Also, creatinine phosphokinase in TA6/7-Gly/Arg, TA7/7-Gly/Gly, and TA7/7-Gly/Arg had a significant increase. Conclusions The present findings showed that the TA7/7 promoter of UGT1A1 gene accounted for a considerable number of Gilbert’s syndrome cases (11.3%). The studied variations had a significant effect on creatine phosphokinase and serum total bilirubin levels.