H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal.
Centro de Investigação em Saúde de Angola (CISA), Caxito, Angola.
Int J Environ Res Public Health. 2021 May 19;18(10):5417. doi: 10.3390/ijerph18105417.
Sickle cell anemia (SCA) is an inherited blood disorder that affects over 300,000 newborns worldwide every year, being particularly prevalent in Sub-Saharan Africa. Despite being a monogenic disease, SCA shows a remarkably high clinical heterogeneity. Several studies have already demonstrated the existence of some polymorphisms that can provide major clinical benefits, producing a mild phenotype. Moreover, the existence of distinct haplotypes can also influence the phenotype patterns of certain populations, leading to different clinical manifestations. Our aim was to assess the association between polymorphisms in genes previously related to SCA disease severity in an Angolan pediatric population.
This study analyzed clinical and biological data collected from 192 Angolan children. Using NGS data, we classified the HBB haplotypes based on four previously described SNPs (rs3834466, rs28440105, rs10128556, and rs968857) and the genotype for the SNPs in HBG2 (rs7482144), BCL11A (rs4671393, rs11886868, rs1427407, rs7557939), HBS1L-MYB (rs66650371) and BGLT3 (rs7924684) genes.
The CAR haplotype was undoubtedly the most common HBB haplotype in our population. The HbF values and the ratio of gamma chains were statistically significant for almost all of the variants studied. We reported for the first time an association between rs7924684 in the BGLT3 gene and gamma chains ratio.
The current findings emphasize the importance personalized medicine would have if applied to SCA patient care, since some of the variants studied might predict the phenotype and the overall response to treatment.
镰状细胞贫血症（SCA）是一种遗传性血液疾病，每年在全球影响超过 30 万新生儿，尤其在撒哈拉以南非洲地区更为普遍。尽管 SCA 是一种单基因疾病，但它表现出显著的临床异质性。已有多项研究表明，一些多态性的存在可以提供重要的临床益处，产生轻度表型。此外，不同的单倍型也会影响某些人群的表型模式，导致不同的临床表现。我们的目的是评估先前与 SCA 疾病严重程度相关的基因多态性在安哥拉儿科人群中的相关性。
本研究分析了从 192 名安哥拉儿童中收集的临床和生物学数据。使用 NGS 数据，我们根据四个先前描述的 SNP（rs3834466、rs28440105、rs10128556 和 rs968857）和 HBG2 基因的 SNP（rs7482144）、BCL11A 基因的 SNP（rs4671393、rs11886868、rs1427407、rs7557939）、HBS1L-MYB 基因的 SNP（rs66650371）和 BGLT3 基因的 SNP（rs7924684）对 HBB 单倍型进行分类。
在我们的人群中，CAR 单倍型无疑是最常见的 HBB 单倍型。HbF 值和γ链的比率对于几乎所有研究的变体都是有统计学意义的。我们首次报道了 BGLT3 基因中的 rs7924684 与γ链比率之间的关联。
目前的研究结果强调了个性化医学在 SCA 患者治疗中的重要性，因为一些研究的变体可能预测表型和整体治疗反应。
