Department of Pathology, College of Medicine, University of Duhok, Duhok, Iraq.
Department of Hematology, Azadi Teaching Hospital, Duhok, Iraq.
Int J Lab Hematol. 2019 Feb;41(1):87-93. doi: 10.1111/ijlh.12927. Epub 2018 Sep 14.
Fetal hemoglobin (HbF) is the major modifier for sickle cell disease (SCD) severity. HbF is modulated mainly by three major quantitative trait loci (QTL) on chromosomes 2, 6, and 11.
Five SNPs in the three QTLs (HBG2, rs7482144; BCL11A, rs1427407 and rs10189857; and HBS1L-MYB intergenic region, rs28384513 and rs9399137) were investigated by multiplex PCR and reverse hybridization, and their roles in HbF and clinical phenotype variability in Iraqi Kurds with SCD were assessed.
HBG2 rs7482144 with minor allele frequency (MAF) of 0.133 was the most significant contributor to HbF variability, contributing 18.1%, followed by rs1427407 (MAF of 0.266) and rs9399137 (MAF of 0.137) at 14.3% and 8.8%, respectively. The other two SNPs were not significant contributors. Furthermore, when the cumulative numbers of minor alleles in the three contributing SNPs were assessed, HbF% and hemoglobin concentration increased with increasing number of minor alleles (P < 0.0005 and 0.001, respectively), while serum lactic dehydrogenase, reticulocytes, leukocytes, transfusion, and pain frequencies decreased (P = 0.003, 0.004, <0.0005, <0.0005, and 0.017, respectively).
It was demonstrated that SNPs in all three major HbF QTLs contribute significantly to HbF and clinical variability in Iraqi Kurds with SCD and that the cumulative number of minor alleles at contributing SNPs may serve as a better predictor of such variability in this population.
胎儿血红蛋白 (HbF) 是影响镰状细胞病 (SCD) 严重程度的主要修饰因子。HbF 主要受染色体 2、6 和 11 上的三个主要数量性状位点 (QTL) 调节。
通过多重 PCR 和反向杂交研究了三个 QTL（HBG2、rs7482144；BCL11A、rs1427407 和 rs10189857；以及 HBS1L-MYB 基因间区，rs28384513 和 rs9399137）中的五个 SNP，并评估了它们在伊拉克库尔德 SCD 患者中对 HbF 和临床表型变异性的作用。
具有较小等位基因频率 (MAF) 为 0.133 的 HBG2 rs7482144 是 HbF 变异性的最显著贡献者，贡献了 18.1%，其次是 rs1427407（MAF 为 0.266）和 rs9399137（MAF 为 0.137），分别为 14.3%和 8.8%。其他两个 SNP 没有显著贡献。此外，当评估三个贡献 SNP 中少数等位基因的累积数量时，HbF%和血红蛋白浓度随着少数等位基因数量的增加而增加（P < 0.0005 和 0.001，分别），而血清乳酸脱氢酶、网织红细胞、白细胞、输血和疼痛频率降低（P = 0.003、0.004、<0.0005、<0.0005 和 0.017，分别）。
研究表明，SCD 伊拉克库尔德人三个主要 HbF QTL 中的 SNP 显著影响 HbF 和临床变异性，贡献 SNP 中的少数等位基因累积数可能更好地预测该人群的这种变异性。
