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Influence of UGT1A1 promoter polymorphism, α-thalassemia and β s haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort.
- Source :
-
Annals of hematology [Ann Hematol] 2021 Apr; Vol. 100 (4), pp. 903-911. Date of Electronic Publication: 2021 Feb 01. - Publication Year :
- 2021
-
Abstract
- Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and β <superscript>S</superscript> haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and β <superscript>S</superscript> haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with β <superscript>S</superscript> haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.
- Subjects :
- Adolescent
Adult
Aged
Alleles
Anemia, Sickle Cell complications
Anemia, Sickle Cell enzymology
Anemia, Sickle Cell genetics
Child
Child, Preschool
Cholelithiasis blood
Cholelithiasis genetics
Female
Fetal Hemoglobin analysis
Genotype
Gilbert Disease enzymology
Gilbert Disease genetics
Glucuronosyltransferase genetics
Haplotypes genetics
Hemolysis
Humans
Hyperbilirubinemia enzymology
Hyperbilirubinemia etiology
Hyperbilirubinemia genetics
Male
Middle Aged
Young Adult
alpha-Thalassemia complications
alpha-Thalassemia enzymology
alpha-Thalassemia genetics
Anemia, Sickle Cell blood
Bilirubin blood
Cholelithiasis etiology
Gilbert Disease blood
Glucuronosyltransferase physiology
Promoter Regions, Genetic genetics
alpha-Thalassemia blood
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0584
- Volume :
- 100
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Annals of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 33523291
- Full Text :
- https://doi.org/10.1007/s00277-021-04422-1