title: 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 bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in a group of 153 young SCD patients (mean age 12.0 +/- 9.0 years) predominantly of Bantu beta S haplotype. The concomitant effect of alpha 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, gender 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 alpha thalassaemia. Thus, the UGT1A1 promoter polymorphism may represent an important nonglobin genetic modifier of Bantu SCD patients' clinical manifestations, even at a young age.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Avenida Padre Cruz, 1649-016, Lisboa, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Martins
authors.affiliation: Serviço de Pediatria, Hospital de Santa Maria (HSM), Lisboa, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Morais
authors.affiliation: Serviço de Pediatria, Hospital Fernando Fonseca, Amadora, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dias
authors.affiliation: Serviço de Pediatria, Hospital Garcia de Orta, Almada, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Soares
authors.affiliation: Serviço de Medicina I-D, HSM, Lisboa, Portugal.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Rolão
authors.affiliation: Serviço de Medicina I-D, HSM, Lisboa, Portugal.
authors.forename: J L
authors.initials: JL
authors.lastname: Ducla-Soares
authors.affiliation: Serviço 1, Medicina, Hospital Dona Estefânia, Lisboa, Portugal.
authors.forename: Lígia
authors.initials: L
authors.lastname: Braga
authors.affiliation: Centro de Biopatologia, INSA, Lisboa, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Seixas
authors.affiliation: Observatório Nacional de Saúde, INSA, Lisboa, Portugal.
authors.forename: Baltazar
authors.initials: B
authors.lastname: Nunes
authors.affiliation: Hospital da Força Aérea, Lisboa, Portugal.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Olim
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Avenida Padre Cruz, 1649-016, Lisboa, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Romão
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Avenida Padre Cruz, 1649-016, Lisboa, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lavinha
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Avenida Padre Cruz, 1649-016, Lisboa, Portugal. paula.faustino@insa.min-saude.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Faustino
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002769:Cholelithiasis / Q000209:etiology; D018900:Dinucleotide Repeats; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017085:alpha-Thalassemia / Q000201:enzymology / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme