Uridine diphosphate glucuronosyl transferase 1A (UGT1A1) promoter polymorphism in young patients with sickle cell anaemia: report of the first cohort study from Nigeria

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. Methods The 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. Results Four (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). Conclusion This 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.

Diagnostic Accuracy of HemotypeSC as a Point-of-Care Testing Device for Sickle Cell Disease: Findings from a Southwestern State in Nigeria and Implications for Patient Care in Resource-Poor Settings of sub-Saharan Africa

“…Parents and guardians of participants in a previous study on the clinical evolution of SCD among a young Nigerian cohort 17 at the study center were contacted through their telephone numbers and were asked to bring their wards for testing with the HemoTypeSC™ kits. The purpose of the study and the procedures were explained to the parents and participants in plain language.…”

Influence of beta-cluster haplotypes, alpha-gene status and UGTA1 polymorphism on clinical and hematological data in sickle-cell disease children from French Guiana

“…Four alleles are described in humans: (TA)5, (TA)6, (TA)7 and (TA)8. Low activity has been reported in humans with (TA) 7/7, 7/8 and 8/8 and normal or high activity in (TA) 6/6, 5/5, 5/6) [13]. The first part of this study showed that the most frequent β S haplotypes were the Benin haplotype (65.9% of the chromosomes) and the Bantu (20.5%) haplotype.…”

Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

“…Initially, the literature search retrieved 1135 published articles. After exclusion of studies because of irrelevance and insufficient data to estimate the outcomes of interest, a total of 34 eligible studies published from 1977 to 2020, which met the eligibility for data extraction and analyses, were used for qualitative and quantitative synthesis; 15 studies from Africa, 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 seven studies from the South America and North America, 42 , 43 , 44 , 45 , 46 , 47 , 48 seven studies from Asia, 8 , 49 , 50 , 51 , 52 , 53 , 54 and four studies from Europe. 55 , 56 , 57 , 58 Overall, this analysis included a total of 6771 SCD patients.…”