Chaouch Leila, Moumni Imen, Ouragini Houyem, Darragi Imen, Kalai Miniar, Chaouachi Dorra, Boudrigua Imen, Hafsia Raouf, Abbes Salem
a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
b Université de Tunis El Manar, Hopital Aziza Othmena, d'Hématologie Clinique , Tunisia.
Hematology. 2016 Aug;21(7):425-9. doi: 10.1080/10245332.2015.1107275. Epub 2016 Jan 22.
Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia (SCA) by inhibiting deoxy sickle hemoglobin (HbS) polymerization. HbF genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Herein, we aimed to determine whether two functional polymorphisms of BCL11A are implicated in the variation of HbF and clinical events in SCA Tunisian patients.
The studied population consisted of 148 SCA patients with SS phenotype. The group of patients was divided into two subgroups according to the threshold point of %HbF which is 15%. Genotyping of rs11886868 and rs4671393 was performed using PCR/Sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between 'group who had %HbF < 15' and 'group who had %HbF >15' (controls) were compared using Pearson's chi-square test (compare 2, version 1.02). The association of each genotype and the combined genotype with complications was performed by logistic regression test.
Our findings showed that the majority of patients carried genotype CT of rs11886868 and genotypes AG and GG of rs4671393 present HbF level < 15%. RR = 0.08, RR = 0.176, and RR = 0.189, respectively. The results showed a significant association between the alleles T of rs11886868 and G of rs4671393 and %HbF < 15% with P = 0.016; RR = 0.39 and P = 8.9 × 10(-3): RR = 0.567, respectively. Interestingly, the C allele of the rs11886868 and the A allele of the rs46713939 were associated with an ameliorated phenotype in patient's SCA. The combination of the genotypes GG and CT explains more phenotypic variance than the sum of the two BCL11A SNPs taken individually.
胎儿血红蛋白（HbF）通过抑制脱氧镰状血红蛋白（HbS）聚合来调节镰状细胞贫血（SCA）的表型。HbF基因受遗传调控，HbF水平及其在镰状红细胞中的分布高度可变。在此，我们旨在确定BCL11A的两个功能多态性是否与突尼斯SCA患者的HbF变化及临床事件有关。
研究人群包括148例SS表型的SCA患者。根据HbF百分比的阈值点15%将患者组分为两个亚组。使用PCR/测序对rs11886868和rs4671393进行基因分型。为了测试性状与候选单核苷酸多态性（SNP）的关联，使用Pearson卡方检验（比较2，版本1.02）比较“HbF百分比<15%的组”和“HbF百分比>15%的组”（对照组）之间的基因型和等位基因频率。通过逻辑回归检验进行每种基因型和组合基因型与并发症的关联分析。
我们的研究结果表明，大多数患者携带rs11886868的CT基因型以及rs4671393的AG和GG基因型，其HbF水平<15%。相对风险（RR）分别为0.08、0.176和0.189。结果显示，rs11886868的T等位基因和rs4671393的G等位基因与HbF百分比<15%之间存在显著关联，P = 0.016；RR = 0.39，以及P = 8.9×10^(-3)：RR = 0.567。有趣的是，rs11886868的C等位基因和rs46713939的A等位基因与SCA患者的表型改善有关。与单独考虑的两个BCL11A SNP的总和相比，GG和CT基因型的组合解释了更多的表型变异。
