Early Complication in Sickle Cell Anemia Children due to A(TA)(n)TAA Polymorphism at the Promoter of UGT1A1 Gene

Aim. To determine the implication of the polymorphism, namely, A(TA)(n)TAA of UGT1A1 in lithogenesis for the first time in Tunisia among sickle cell anemia (SCA) children patients. Material and Methods. Our study was performed in 2010 and it involved 76 subjects chosen as control group characterized with normal hemoglobin status and presence of cholelithiasis and 102 SCA pediatric patients among whom 52 have cholelithiasis. We analyzed the polymorphism A(TA)(n)TAA at the UGT1A1 promoter and the relationships between the various A(TA)(n)TAA genotypes and alleles and bilirubin levels and occurrence of cholelithiasis. Results and Discussion. The repartition of genotypes found according to serum bilirubin level shows a significant association between genotypes carrying variant (TA)(7) and hyperbilirubinemia (P < 0.05). We demonstrated the association of two genotypes with gallstones formation among SCA children patients: (TA)(7)/(TA)(7) and (TA)(7)/(TA)(8) with P = 8.1 × 10(−8) and P = 0.01, respectively. (TA)(7) and (TA)(8) allele variants act as a risk factor for early gallstones formation in SCA patients with P = 5.8 × 10(−9) and P = 0.01, respectively. As for the control group only the genotype (TA)(7)/(TA)(7) presented a risk factor for gallstones formation. Conclusion. The novelty of this report is that it is the first time that a similar study was made on the Tunisian children sickle cell population and that the results show a clear association of (TA)(7) variant in early gallstones formation in Tunisian SCA children. Interestingly our findings highlighted the association of (TA)(8) variant as well, which was not found in previous studies.