Fong Cristian, Menzel Stephan, Lizarralde María Alejandra, Barreto Guillermo
Grupo de Genética Molecular Humana, Sección de Genética, Departamento de Biología, Universidad del Valle.
King's College London, School of Medicine, The James Black Centre, , London, England, United Kingdom.
Biomedica. 2015 Jul-Sep;35(3):437-43. doi: 10.7705/biomedica.v35i3.2573.
Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies.
We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia.
Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations.
We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population.
These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.
胎儿血红蛋白是调节镰状细胞贫血严重程度的一个重要因素。其在外周血中的水平具有很强的遗传决定性。与胎儿血红蛋白水平升高相关的基因座表现出群体特异性等位基因频率。
我们调查了60例哥伦比亚镰状细胞贫血患者中促进胎儿血红蛋白持续存在的已知常见基因变异（rs11886868、rs9399137、rs4895441和rs7482144）的存在情况及影响。
通过限制性片段长度多态性（RFLP）和TaqMan技术对四个单核苷酸多态性（SNP）进行基因分型。使用氧合血红蛋白碱性变性技术对这些患者的胎儿血红蛋白（HbF）进行定量。将基因型频率与全球参考人群中报告的频率进行比较。
我们在这四个SNP中检测到了基因变异，据报道这四个SNP在哥伦比亚患者中均与较高的HbF水平相关。SNP与HbF水平之间的遗传关联未达到统计学意义。这些变异的频率反映了我们患者群体的特定种族构成：rs7482144 - 'A'的高患病率反映了镰状细胞突变的西非起源，而rs4895441 - 'G'和rs11886868 - 'C'的高频率表明美洲印第安人种族背景对哥伦比亚镰状细胞病群体有重大影响。
这些结果表明，在哥伦比亚的镰状细胞病群体中不存在单一的遗传背景，而是有两种（非洲和美洲印第安人）。这种独特的遗传情况将为进一步研究这些基因座提供机会，如精细定位和分子生物学研究。预计哥伦比亚患者将为镰状细胞病修饰基因座的作用提供独特的见解。
