Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Department of Medicine, King Fahd Hospital, Alomran Scientific Chair, King Faisal University, Al-Ahssa, Saudi Arabia.
Hemoglobin. 2020 Mar;44(2):78-81. doi: 10.1080/03630269.2020.1739068. Epub 2020 May 25.
Hb F modulates sickle cell disease. Five major haplotypes of the β-globin gene cluster are associated with sickle cell disease. In the Eastern Province of Saudi Arabia, the Arab-Indian (AI) is most common. Single nucleotide polymorphism (SNP) genotyping (rs3834466, rs28440105, rs10128556, and rs968857) was carried out by nuclease allelic discrimination assay with target-specific forward and reverse primers, TaqMan probes, labeled with VIC and FAM. In 778 patients with sickle cell disease from the Eastern Province, a haplotype was assigned to 90.9% of all samples; 9.1% were classified as compound heterozygotes for the AI and an atypical haplotype. The distribution of haplotypes for 746 Hb S (: c.20A > T) homozygotes was: 614 AI/AI, nine SEN/SEN (Senegal), 42 SEN/AI, nine CAM/CAM (Cameroon), one CAR (Central African Republic)/BEN (Benin), 71 AI/atypical. In Hb S/β-thalassemia (Hb S/β-thal), the distribution of Hb S haplotypes was: 22 AI/AI, one CAM/CAM, four AI/SEN, five AI/atypical. Mean Hb F in the haplotypes was: AI/AI 16.6 ± 7.5%, CAM/CAM 8.0 ± 4.1%, SEN/SEN 11.0 ± 5.1%, SEN/AI 15.1 ± 4.6%, AI/atypical 16.2 ± 6.5%. The presence of the SEN and CAM haplotypes was unexpected due to the apparent homogeneity of the population of the Eastern Province. We have successfully classified sickle cell disease haplotypes using the relatively inexpensive TaqMan assay for the first time. In addition, we have previously shown that children with AI haplotype have Hb F of 30.0% and mild disease, while in our cohort of adult AI patients, which might be the largest yet reported, Hb F was about 16.6%.
血红蛋白 F 调节镰状细胞病。β-球蛋白基因簇的五个主要单倍型与镰状细胞病有关。在沙特阿拉伯东部省，阿拉伯-印度人（AI）是最常见的。通过核酶等位基因区分测定法对单核苷酸多态性（SNP）基因分型（rs3834466、rs28440105、rs10128556 和 rs968857）进行了研究，该方法使用了针对特定目标的正向和反向引物、TaqMan 探针，探针用 VIC 和 FAM 进行标记。在东部省 778 名镰状细胞病患者中，90.9%的所有样本都分配了单倍型；9.1%的患者被归类为 AI 和非典型单倍型的复合杂合子。746 名 Hb S（：c.20A > T）纯合子的单倍型分布为：614 AI/AI、9 个 SEN/SEN（塞内加尔）、42 SEN/AI、9 个 CAM/CAM（喀麦隆）、1 个 CAR（中非共和国）/BEN（贝宁）、71 AI/非典型。在 Hb S/β-地中海贫血（Hb S/β-thal）中，Hb S 单倍型的分布为：22 AI/AI、1 个 CAM/CAM、4 个 AI/SEN、5 个 AI/非典型。单倍型中平均 Hb F 为：AI/AI 16.6 ± 7.5%、CAM/CAM 8.0 ± 4.1%、SEN/SEN 11.0 ± 5.1%、SEN/AI 15.1 ± 4.6%、AI/非典型 16.2 ± 6.5%。由于东部省人口明显同质，SEN 和 CAM 单倍型的存在出人意料。我们首次使用相对廉价的 TaqMan 测定法成功地对镰状细胞病单倍型进行了分类。此外，我们之前已经表明，具有 AI 单倍型的儿童的 Hb F 为 30.0%，疾病较轻，而在我们的 AI 成年患者队列中，Hb F 约为 16.6%，这可能是迄今为止报告的最大队列。
