Abstract
Background(TA) n repeat sequence (rs8175347) of UGT1A1 gene promoter polymorphism is associated with serum bilirubin levels and gallstones among different sickle cell anaemia (SCA) populations. There are no data on UGT1A1 polymorphisms and their impact on Nigerian SCA patients. In this study, we determined the distribution of the UGT1A1 (TA) n genotypes among a group of young Nigerian SCA patients and healthy controls. In addition, the influence of UGT1A1 (TA) n genotypes on the laboratory and clinical events among the patients was determined.MethodsThe distribution of the UGT1A1 (TA) n genotypes among 101 young Nigerian SCA patients and 64 normal appropriate controls were determined and studied. The UGT1A1 (TA) n genotypes were further classified into subgroups and used to differentiate the clinical events and laboratory parameters of the patients.ResultsFour (TA) n alleles:(TA)5, 6, 7, and 8 were found. These were associated with 10 genotypes: TA5/5, 5/6, 5/7, 5/8, 6/6, 6/7, 6/8, 7/7, 7/8, 8/8. The normal (wild-type)-(TA) 6/6), low- (TA) 7/7, 7/8, 8/8), intermediate- (TA) 5/7, 5/8, 6/7, 6/8), and high-activity (TA) 5/5, 5/6,) genotypes were found in 24.8, 24.8, 41.5, and 8.9% patients and 20.3, 15.6, 61, and 3.1% controls respectively. The general genotype distribution of the patients and control group were not significantly different. There were significant differences in serum bilirubin and lactate dehydrogenase (LDH) of the patients when differentiated by the UGT1A1 (TA) n genotypes (p<0.05). Asymptomatic gallstones were found in 5.9% of patients and were significantly of the low-activity genotypes sub-group 5 (20%) vs 1(1.3%) p = 0.0033. Although, bilirubin and fetal hemoglobin (HbF) of patients with gallstones were significantly different from those without gallstone, only the serum bilirubin was associated with UGT1A1 (TA) n genotypes on multivariate analysis (p < 0.0001).ConclusionThis study highlights the contribution of UGT1A1 polymorphisms, a non-globin genetic factor, to the laboratory and clinical manifestations of young Nigerian SCA patients for the first time. It also shows that children with co-inheritance of low UGT1A1 (TA) n affinity genotypes may be at risk of gallstone, hence the need to follow them up.
Highlights
Sickle cell disease (SCD) is a common genetic disorder among Africans
The aims of this study were to determine the distribution of Uridine diphosphate glucuronosyltransferase 1A isoform 1 (UGT1A1) (TA) n genotypes among a group of young sickle cell anaemia (SCA) patients and healthy controls and determine the influence of the UGT1A1 (TA) n genotypes on the laboratory parameters and clinical events among the young SCA patients
Study participants and settings The study was conducted on 101 hydroxyurea-naïve children and adolescents with SCA (Homozygous SS) aged between 2 and 21 years who are regular attendees at the paediatric haematology unit of the Ekiti State University Teaching Hospital (EKSUTH), Ado Ekiti, Ekiti State, in Southwest Nigeria
Summary
Sickle cell disease (SCD) is a common genetic disorder among Africans. Individuals with the disease have variable clinical expression but homozygosity for the HbS gene, known as sickle cell anaemia (SCA), is the most severe form [1]. Children with SCA have chronic hemolysis, leading to accumulation of serum bilirubin and consequent gallstones [2]. Bilirubin is a tetrapyrol that results from the breakdown of heme in red blood cells. At moderate levels, it protects against oxidative stress and inflammatory injuries, and some infectious diseases [3,4,5]. Excessive bilirubin levels, as seen in chronic hemolysis, have been linked to increased incidence of gallstones [1, 2, 5]. In children with SCA, this risk increases with advancing age with a cumulative incidence of approximately 50% by adulthood and some of them may need cholecystectomy [2, 6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
