División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico.
Departamento de Biología Molecular y Genómica, Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG), Guadalajara, Jalisco, Mexico.
J Trop Pediatr. 2022 Aug 4;68(5). doi: 10.1093/tropej/fmac073.
Hemoglobin S is caused by a nucleotide change in HBB gene (HBB:c.20A>T, p.Glu6Val), is presented in diverse forms: simple carriers (HbSA), homozygotes (HbSS) also known as sickle cell anemia, and compound heterozygotes with other β-hemoglobinopathies. It is worldwide distributed, in Mexico, is frequently observed in the southern states Guerrero, Oaxaca and Chiapas. Elevated fetal hemoglobin (HbF) is associated with mild phenotype; single-nucleotide variants (SNVs) in modifier genes, such as BCL11A, HBG2, HBBP1 pseudogene and HBS1L-MYB intergenic region, upregulate HbF synthesis. The aim of this study was to identify HbF regulating genetic variants in HbSS and HbSA Mexican subjects. We studied 39 individuals (HbSS = 24, 61%, HbSA = 15, 39%) from Chiapas (67%) and Guerrero (33%), peripheral blood was collected in ethylenediamine tetraacetic acid (EDTA) for molecular and hematological studies, DNA was isolated by salting-out technic and genotyping was performed through allelic discrimination by real time polymerase chain reaction (RT-PCR) using Taqman® probes for 15 SNV (in BCL11A: rs6706648, rs7557939, rs4671393, rs11886868, rs766432, rs7599488, rs1427407; HBS1L-MYB: rs28384513, rs7776054, rs9399137, rs4895441, rs9402686, rs1320963; HBG2: rs7482144; and HBBP1: rs10128556). The obtained data were analyzed using IMB SPSS v.22.0 software. All minor alleles were observed in frequencies over 0.05, the most frequent was rs9402686 (0.82), while the less frequent was rs101028556 (0.08). In HbSS group, the mean fetal hemoglobin was 11.9 ± 5.9% and was significantly elevated in BCL11A rs11886868 wildtype homozygotes and in carriers of HBS1L-MYB intergenic region rs7776054 (p = 0.04 and p = 0.03, respectively). In conclusion, in HbSS Mexican patients, two SNVs were observed related to increased HbF; BCL11A rs11886868 and HBS1L-MYB rs7776054.
血红蛋白 S 是由 HBB 基因（HBB:c.20A>T，p.Glu6Val）中的核苷酸变化引起的，表现为多种形式：单纯携带者（HbSA）、纯合子（HbSS），也称为镰状细胞贫血，以及与其他β-血红蛋白病的复合杂合子。它在全球范围内分布，在墨西哥，在格雷罗州、瓦哈卡州和恰帕斯州等南部各州经常观察到。胎儿血红蛋白（HbF）水平升高与轻度表型相关；修饰基因中的单核苷酸变异（SNV），如 BCL11A、HBG2、HBBP1 假基因和 HBS1L-MYB 基因间区，可上调 HbF 合成。本研究的目的是鉴定墨西哥 HbSS 和 HbSA 个体中调节 HbF 的遗传变异。我们研究了来自恰帕斯州（67%）和格雷罗州（33%）的 39 名个体（HbSS=24，61%，HbSA=15，39%），采集外周血于乙二胺四乙酸（EDTA）中，用于分子和血液学研究，用盐析技术分离 DNA，并通过实时聚合酶链反应（RT-PCR）中的等位基因鉴别技术进行基因分型，使用 Taqman®探针对 15 个 SNV 进行检测（BCL11A：rs6706648、rs7557939、rs4671393、rs11886868、rs766432、rs7599488、rs1427407；HBS1L-MYB：rs28384513、rs7776054、rs9399137、rs4895441、rs9402686、rs1320963；HBG2：rs7482144；和 HBBP1：rs10128556）。使用 IMB SPSS v.22.0 软件分析获得的数据。所有的次要等位基因的频率均超过 0.05，最常见的是 rs9402686（0.82），而最少见的是 rs101028556（0.08）。在 HbSS 组中，胎儿血红蛋白平均值为 11.9±5.9%，在 BCL11A rs11886868 野生型纯合子和 HBS1L-MYB 基因间区 rs7776054 携带者中显著升高（p=0.04 和 p=0.03）。总之，在墨西哥 HbSS 患者中，观察到两个与 HbF 升高相关的 SNV：BCL11A rs11886868 和 HBS1L-MYB rs7776054。
