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.

中文翻译：

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镰状细胞性贫血的年轻患者中尿苷二磷酸葡萄糖醛酸糖基转移酶1A（UGT1A1）启动子多态性：来自尼日利亚的首次队列研究报告。

UGT1A1基因启动子多态性的背景（TA）n重复序列（rs8175347）与不同镰状细胞性贫血（SCA）人群中的血清胆红素水平和胆结石有关。没有有关UGT1A1基因多态性及其对尼日利亚SCA患者的影响的数据。在这项研究中，我们确定了一组尼日利亚青年SCA患者和健康对照人群中UGT1A1（TA）n基因型的分布。此外，确定了UGT1A1（TA）n基因型对患者实验室和临床事件的影响。方法确定和研究UGT1A1（TA）n基因型在101名尼日利亚年轻SCA患者和64名正常人中的分布。UGT1A1（TA）n基因型进一步分为亚组，用于区分患者的临床事件和实验室参数。结果发现4个（TA）n等位基因：（TA）5、6、7和8。这些与10个基因型相关：TA5 / 5、5 / 6、5 / 7、5 / 8、6 / 6、6 / 7、6 / 8、7 / 7、7 / 8、8 / 8。普通（野生型）-（TA）6/6），低-（TA）7 / 7、7 / 8、8 / 8），中-（TA）5 / 7、5 / 8、6 / 7 ，6/8）和高活性（TA）5 / 5、5 / 6，）基因型分别在24.8、24.8、41.5和8.9％的患者以及20.3、15.6、61和3.1％的对照组中发现。患者和对照组的一般基因型分布没有显着差异。用UGT1A1（TA）n基因型区分患者的血清胆红素和乳酸脱氢酶（LDH）有显着差异（p <0.05）。在5.9％的患者中发现了无症状的胆结石，其中低活性基因型的亚组5（20％）与1（1.3％）显着相关，p = 0.0033。尽管有胆结石的患者的胆红素和胎儿血红蛋白（HbF）与无胆结石的患者有显着差异，但在多变量分析中，只有血清胆红素与UGT1A1（TA）n基因型相关（p <0.0001）。结论本研究首次突出了非球蛋白遗传因子UGT1A1多态性对尼日利亚年轻SCA患者的实验室和临床表现的贡献。它还表明，具有低UGT1A1（TA）n亲和力基因型共同遗传力的儿童可能有胆结石的风险，因此需要跟进他们。尽管有胆结石的患者的胆红素和胎儿血红蛋白（HbF）与无胆结石的患者有显着差异，但在多变量分析中，只有血清胆红素与UGT1A1（TA）n基因型相关（p <0.0001）。结论本研究首次突出了非球蛋白遗传因子UGT1A1多态性对尼日利亚年轻SCA患者的实验室和临床表现的贡献。它还表明，具有低UGT1A1（TA）n亲和力基因型共同遗传力的儿童可能有胆结石的风险，因此需要跟进他们。尽管有胆结石的患者的胆红素和胎儿血红蛋白（HbF）与无胆结石的患者有显着差异，但在多变量分析中，只有血清胆红素与UGT1A1（TA）n基因型相关（p <0.0001）。结论本研究首次突出了非球蛋白遗传因子UGT1A1多态性对尼日利亚年轻SCA患者的实验室和临床表现的贡献。它还表明，具有低UGT1A1（TA）n亲和力基因型共同遗传力的儿童可能有胆结石的风险，因此需要跟进他们。结论本研究首次突出了非球蛋白遗传因子UGT1A1多态性对尼日利亚年轻SCA患者的实验室和临床表现的贡献。它还表明，具有低UGT1A1（TA）n亲和力基因型共同遗传力的儿童可能有胆结石的风险，因此需要跟进他们。结论本研究首次突出了非球蛋白遗传因子UGT1A1多态性对尼日利亚年轻SCA患者的实验室和临床表现的贡献。它还表明，具有低UGT1A1（TA）n亲和力基因型共同遗传力的儿童可能有胆结石的风险，因此需要跟进他们。