Abstract：
BACKGROUND: Sickle cell disease (SCD) is a major heritable genetic disease in sub-Saharan Africa, including Mauritania. Fetal hemoglobin (HbF) can affect the pathophysiology, moderate the clinical course, and offer prospects for curative treatment of SCD. This study aimed to investigate the influence of single nucleotide polymorphisms (SNPs) in the BCL11A gene on the levels of HbF and hematological parameters in Mauritanian sickle cell (HbSS) patients.
METHODS: Complete blood count was assessed in 565 patients suspected to have SCD. Polymerase chain reaction (PCR)-restriction fragment length polymorphism was performed to identify the HbSS, and sequencing was used for genotyping three SNPs: rs4671393 (A>G) and rs11886868 (C>T) in the intron 2 and rs1052520 (G>A) in the 3\'UTR regions of the BCL11A gene in 50 sickle cell patients.
RESULTS: The prevalence of HbSS among the study population was 8.8% (50/565), and the mean (± standard deviation) of HbF level was 15.0% (± 6.0%). Sequencing showed the presence of three genotypes: AA (13.6%), AG (46.6%), GG (39.6%) in rs4671393; CC (17.6%), CT (48.7%), and TT (33.6%) in rs11886868. All samples from HbSS individuals displayed a wild-type genotype in the rs1052520 allele. The prevalence of minor alleles A (rs4671393) and C (rs11886868) were 37% and 39%, respectively. There was a statistically significant association (p = 0.034) between rs4671393 SNP and elevated HbF (mean 12.72 ± 6.26%).
CONCLUSIONS: The study of three SNPs in the BCL11A locus in Mauritanian patients with SCD showed a significant association of rs4671393 allele with the HbF level. Further research is needed to explore additional SNPs in the BCL11A locus and investigate other genetic markers reported to modulate HbF levels, such as HBS1L-MYB and Xmn1-HBG2, to improve the management of this potentially life-threatening condition in Mauritania.
METHODS: Complete blood count was assessed in 565 patients suspected to have SCD. Polymerase chain reaction (PCR)-restriction fragment length polymorphism was performed to identify the HbSS, and sequencing was used for genotyping three SNPs: rs4671393 (A>G) and rs11886868 (C>T) in the intron 2 and rs1052520 (G>A) in the 3\'UTR regions of the BCL11A gene in 50 sickle cell patients.
RESULTS: The prevalence of HbSS among the study population was 8.8% (50/565), and the mean (± standard deviation) of HbF level was 15.0% (± 6.0%). Sequencing showed the presence of three genotypes: AA (13.6%), AG (46.6%), GG (39.6%) in rs4671393; CC (17.6%), CT (48.7%), and TT (33.6%) in rs11886868. All samples from HbSS individuals displayed a wild-type genotype in the rs1052520 allele. The prevalence of minor alleles A (rs4671393) and C (rs11886868) were 37% and 39%, respectively. There was a statistically significant association (p = 0.034) between rs4671393 SNP and elevated HbF (mean 12.72 ± 6.26%).
CONCLUSIONS: The study of three SNPs in the BCL11A locus in Mauritanian patients with SCD showed a significant association of rs4671393 allele with the HbF level. Further research is needed to explore additional SNPs in the BCL11A locus and investigate other genetic markers reported to modulate HbF levels, such as HBS1L-MYB and Xmn1-HBG2, to improve the management of this potentially life-threatening condition in Mauritania.
摘要：
背景：镰状细胞病（SCD）是撒哈拉以南非洲的一种主要遗传病，包括毛里塔尼亚。胎儿血红蛋白（HbF）可以影响病理生理学，缓和临床过程，并为SCD的治疗提供了前景。本研究旨在探讨BCL11A基因中的单核苷酸多态性（SNPs）对毛里塔尼亚镰状细胞（HbSS）患者HbF水平和血液学参数的影响。
方法：对565例疑似SCD患者进行全血细胞计数评估。进行聚合酶链反应（PCR）-限制性片段长度多态性以鉴定HbSS，并对50例镰状细胞患者的内含子2中的rs4671393(A>G)和rs11886868(C>T)和BCL11A基因3个UTR区的rs1052520(G>A)进行基因分型。
结果：研究人群中HbSS的患病率为8.8%（50/565），HbF水平的平均值(±标准差)为15.0%(±6.0%)。测序显示存在三种基因型:AA(13.6%),AG（46.6%），GG(39.6%)在rs4671393;CC(17.6%),CT（48.7%），rs11886868中的TT（33.6%）。来自HbSS个体的所有样品在rs1052520等位基因中显示野生型基因型。次要等位基因A(rs4671393)和C(rs11886868)的患病率分别为37%和39%,分别。rs4671393SNP与升高的HbF之间存在统计学上的显着关联（p=0.034）（平均12.72±6.26％）。
结论：对毛里塔尼亚SCD患者BCL11A基因座中三个SNP的研究显示rs4671393等位基因与HbF水平显著相关。需要进一步的研究来探索BCL11A基因座中的其他SNP，并调查据报道调节HbF水平的其他遗传标记。例如HBS1L-MYB和Xmn1-HBG2，以改善毛里塔尼亚这种潜在威胁生命的疾病的管理。
方法：对565例疑似SCD患者进行全血细胞计数评估。进行聚合酶链反应（PCR）-限制性片段长度多态性以鉴定HbSS，并对50例镰状细胞患者的内含子2中的rs4671393(A>G)和rs11886868(C>T)和BCL11A基因3个UTR区的rs1052520(G>A)进行基因分型。
结果：研究人群中HbSS的患病率为8.8%（50/565），HbF水平的平均值(±标准差)为15.0%(±6.0%)。测序显示存在三种基因型:AA(13.6%),AG（46.6%），GG(39.6%)在rs4671393;CC(17.6%),CT（48.7%），rs11886868中的TT（33.6%）。来自HbSS个体的所有样品在rs1052520等位基因中显示野生型基因型。次要等位基因A(rs4671393)和C(rs11886868)的患病率分别为37%和39%,分别。rs4671393SNP与升高的HbF之间存在统计学上的显着关联（p=0.034）（平均12.72±6.26％）。
结论：对毛里塔尼亚SCD患者BCL11A基因座中三个SNP的研究显示rs4671393等位基因与HbF水平显著相关。需要进一步的研究来探索BCL11A基因座中的其他SNP，并调查据报道调节HbF水平的其他遗传标记。例如HBS1L-MYB和Xmn1-HBG2，以改善毛里塔尼亚这种潜在威胁生命的疾病的管理。
