Background and Objectives. High levels of erythrocyte destruction in sickle cell anemia (SCA) result in chronic hyperbilirubinemia, with cholelithiasis occurring in a subset of patients. We investigated whether susceptibility to cholelithiasis in SCA was associated with the promoter polymorphism of the 5′-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene encoding a key enzyme in bilirubin catabolism. Design and Methods. We determined the frequencies of UGT1A1 promoter alleles in 171 SCA children and 153 SCA adults regularly followed for a number of years at the Guadeloupe sickle cell center. These patients had undergone liver/biliary tree ultrasound scans every year. We analyzed the relationships between the various UGT1A1 promoter alleles and hemoglobin levels, steady-state total and unconjugated bilirubin concentrations and the frequency of cholelithiasis. Results. In both children and adults, (TA) 6 was less frequent and (TA) 7 more frequent in patients with cholelithiasis than in those without this condition. Total and unconjugated bilirubin levels and the frequency of cholelithiasis were significantly higher in patients with (TA) 7/(TA) 7 and (TA) 7/(TA) 8 genotypes than in those with other genotypes. Those homozygous for (TA) 6 or carrying at least one (TA) 5 allele had the lowest total and unconjugated bilirubin levels and were least likely to have cholelithiasis. Patients with (TA) 6/(TA) 7 and (TA) 6/(TA) 8 genotypes presented intermediate values. Kaplan-Meier analysis of cholelithiasis-free survival in children demonstrated an early age-at-onset for cholelithiasis in patients with (TA) 7/(TA) 7 and (TA) 7/(TA) 8 genotypes. Interpretations and Conclusions. This study shows that the UGT1A1 gene promoter polymorphism is a major genetic risk factor modifying the frequency and age-at-onset of cholelithiasis in SCA patients.
Erythropoietic protoporphyria : genotype, phenotype and fluorocytes count relationship / M.D. Cappellini, E. Di Pierro, V. Moriondo, P. Bonara, E. Patti. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 90:2(2005), pp. 188-188.
Erythropoietic protoporphyria : genotype, phenotype and fluorocytes count relationship
M.D. CappelliniPrimo
;E. Di PierroSecondo
;
2005
Abstract
Background and Objectives. High levels of erythrocyte destruction in sickle cell anemia (SCA) result in chronic hyperbilirubinemia, with cholelithiasis occurring in a subset of patients. We investigated whether susceptibility to cholelithiasis in SCA was associated with the promoter polymorphism of the 5′-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene encoding a key enzyme in bilirubin catabolism. Design and Methods. We determined the frequencies of UGT1A1 promoter alleles in 171 SCA children and 153 SCA adults regularly followed for a number of years at the Guadeloupe sickle cell center. These patients had undergone liver/biliary tree ultrasound scans every year. We analyzed the relationships between the various UGT1A1 promoter alleles and hemoglobin levels, steady-state total and unconjugated bilirubin concentrations and the frequency of cholelithiasis. Results. In both children and adults, (TA) 6 was less frequent and (TA) 7 more frequent in patients with cholelithiasis than in those without this condition. Total and unconjugated bilirubin levels and the frequency of cholelithiasis were significantly higher in patients with (TA) 7/(TA) 7 and (TA) 7/(TA) 8 genotypes than in those with other genotypes. Those homozygous for (TA) 6 or carrying at least one (TA) 5 allele had the lowest total and unconjugated bilirubin levels and were least likely to have cholelithiasis. Patients with (TA) 6/(TA) 7 and (TA) 6/(TA) 8 genotypes presented intermediate values. Kaplan-Meier analysis of cholelithiasis-free survival in children demonstrated an early age-at-onset for cholelithiasis in patients with (TA) 7/(TA) 7 and (TA) 7/(TA) 8 genotypes. Interpretations and Conclusions. This study shows that the UGT1A1 gene promoter polymorphism is a major genetic risk factor modifying the frequency and age-at-onset of cholelithiasis in SCA patients.Pubblicazioni consigliate
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