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.

中文翻译：

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在来自南墨西哥的纯合子 (HbSS) 和杂合子 (HbSA) 受试者中发现的胎儿血红蛋白调节遗传变异。

血红蛋白 S 由 HBB 基因的核苷酸变化 (HBB:c.20A>T, p.Glu6Val) 引起，以多种形式存在：简单携带者 (HbSA)、纯合子 (HbSS) 也称为镰状细胞性贫血，以及复合与其他 β-血红蛋白病的杂合子。它在世界范围内分布，在墨西哥，在南部的格雷罗州、瓦哈卡州和恰帕斯州经常被观察到。升高的胎儿血红蛋白 (HbF) 与轻度表型相关；修饰基因中的单核苷酸变异 (SNV)，例如 BCL11A、HBG2、HBBP1 假基因和 HBS1L-MYB 基因间区域，可上调 HbF 合成。本研究的目的是确定 HbF 调节 HbSS 和 HbSA 墨西哥受试者的遗传变异。我们研究了来自恰帕斯州 (67%) 和格雷罗州 (33%) 的 39 人（HbSS = 24, 61%，HbSA = 15, 39%），将外周血收集在乙二胺四乙酸 (EDTA) 中用于分子和血液学研究，通过盐析技术分离 DNA，并使用 Taqman® 探针对 15 SNV 通过实时聚合酶链反应 (RT-PCR) 等位基因区分进行基因分型(in BCL11A: rs6706648, rs7557939, rs4671393, rs11886868, rs766432, rs7599488, rs1427407; HBS1L-MYB: rs28384513, rs7776054, rs9399137, rs4895441, rs9402686, rs1320963; HBG2: rs7482144; and HBBP1: rs10128556). 使用 IMB SPSS v.22.0 软件分析获得的数据。所有次要等位基因的频率均超过 0.05，频率最高的是 rs9402686 (0.82)，频率最低的是 rs101028556 (0.08)。在 HbSS 组中，平均胎儿血红蛋白为 11.9 ± 5。9%，并且在 BCL11A rs11886868 野生型纯合子和 HBS1L-MYB 基因间区域 rs7776054 的携带者中显着升高（分别为 p = 0.04 和 p = 0.03）。总之，在 HbSS 墨西哥患者中，观察到两个与 HbF 升高相关的 SNV；BCL11A rs11886868 和 HBS1L-MYB rs7776054。