Referral Center for Sickle Cell Disease, Department of Pediatrics, and.
Department of Pediatrics, Centre Hospitalier Intercommunal and University Paris Est, Créteil, France.
Blood Adv. 2018 Mar 27;2(6):626-637. doi: 10.1182/bloodadvances.2017014555.
Sickle cell anemia (SCA), albeit monogenic, has heterogeneous phenotypic expression, mainly related to the level of hemoglobin F (HbF). No large cohort studies have ever compared biological parameters in patients with major β-globin haplotypes; ie, Senegal (SEN), Benin (BEN), and Bantu/Central African Republic (CAR). The aim of this study was to evaluate the biological impact of α genes, β haplotypes, and glucose-6-phosphate dehydrogenase (G6PD) activity at baseline and with hydroxyurea (HU). Homozygous HbS patients from the Créteil pediatric cohort with available α-gene and β-haplotype data were included (n = 580; 301 females and 279 males) in this retrospective study. Homozygous β-haplotype patients represented 74% of cases (37.4% CAR/CAR, 24.3% BEN/BEN, and 12.1% SEN/SEN). HU was given to 168 cohort SCA children. Hematological parameters were recorded when HbF was maximal, and changes (HU-T0) were calculated. At baseline, CAR-haplotype and α-gene numbers were independently and negatively correlated with Hb and positively correlated with lactate dehydrogenase. HbF was negatively correlated with CAR-haplotype numbers and positively with BEN- and SEN-haplotype numbers. The /rs1427407 "T" allele, which is favorable for HbF expression, was positively correlated with BEN- and negatively correlated with CAR-haplotype numbers. With HU treatment, and HbF values were positively correlated with the BEN-haplotype number. BEN/BEN patients had higher HbF and Hb levels than CAR/CAR and SEN/SEN patients. In conclusion, we show that BEN/BEN patients have the best response on HU and suggest that this could be related to the higher prevalence of the favorable /rs1427407/T/allele for HbF expression in these patients.
镰状细胞贫血 (SCA) 虽然是单基因疾病，但表型表现具有异质性，主要与血红蛋白 F (HbF) 水平有关。以前没有研究比较过主要β-珠蛋白单体型（即塞内加尔 (SEN)、贝宁 (BEN) 和中非共和国/班图 (CAR)）患者的生物学参数。本研究旨在评估α基因、β单体型和葡萄糖-6-磷酸脱氢酶 (G6PD) 活性在基线和羟基脲 (HU) 治疗下的生物学影响。本回顾性研究纳入了 Créteil 儿科队列中具有可用α基因和β单体型数据的纯合 HbS 患者（n=580；301 名女性和 279 名男性）。纯合β单体型患者占病例的 74%（37.4% CAR/CAR、24.3% BEN/BEN 和 12.1% SEN/SEN）。168 名队列 SCA 儿童接受 HU 治疗。当 HbF 达到最大值时记录血液学参数，并计算变化值（HU-T0）。基线时，CAR 单体型和α基因数量与 Hb 呈负相关，与乳酸脱氢酶呈正相关。HbF 与 CAR 单体型数量呈负相关，与 BEN 和 SEN 单体型数量呈正相关。有利于 HbF 表达的 rs1427407“T”等位基因与 BEN 单体型数量呈正相关，与 CAR 单体型数量呈负相关。HU 治疗后，Hb 和 HbF 值与 BEN 单体型数量呈正相关。BEN/BEN 患者的 HbF 和 Hb 水平高于 CAR/CAR 和 SEN/SEN 患者。综上所述，我们发现 BEN/BEN 患者对 HU 的反应最好，并提示这可能与这些患者中有利于 HbF 表达的 rs1427407/T/等位基因的高患病率有关。
