Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism 

Abstract 
Elevated erythrocyte destruction in Sickle Cell Disease (SCD) results in chronic hyperbilirubinaemia and, in a subset of patients, cholelithiasis occurs. We investigated whether the (TA)n promoter polymorphism in the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) may modify bilirubin metabolism, influencing the bilirubinaemia, the predisposition to cholelithiasis and subsequent cholecystectomy, in a group of 153 young SCD patients (mean age 12.0 ± 9.0 years) predominantly of Bantu bS haplotype. The concomitant effect of a-thalassaemia was also analysed.
Among the several UGT1A1 genotypes found, the most frequent were the (TA)6/(TA)6 (n=37), (TA)6/(TA)7 (n=60) and (TA)7/(TA)7 (n=29). These groups of patients did not significantly differ in age, sex ratio, and haemoglobin, foetal haemoglobin and reticulocyte levels. On the other hand, total bilirubin levels were significantly different between groups, with an increased (TA) repeat number being associated with higher bilirubinaemia. Furthermore, both cholelithiasis and cholecystectomy were more frequent in groups with higher (TA) repeat number, although the former association was not statistically significant. None of the mentioned parameters is statistically different within UGT1A1 groups with the presence of a-thalassaemia. Thus the UGT1A1 promoter polymorphism may represent an important non-globin genetic modifier of Bantu SCD patients’ clinical manifestations even at a young age.

 

Autores : 

Martins R, Morais A, Dias A, Soares I, Rolão C, Ducla-Soares JL, Braga L, Seixas T, Nunes B, Olim G, Romão L, Lavinha J, Faustino P