Nagel R L, Fabry M E, Pagnier J, Zohoun I, Wajcman H, Baudin V, Labie D
N Engl J Med. 1985 Apr 4;312(14):880-4. doi: 10.1056/NEJM198504043121403.
Patients with sickle cell anemia vary in the hematologic and clinical features of their disease, in part because of variability in the presence of linked and unlinked genes that modify the expression of the disease. The hemoglobin S gene is strongly linked to three different haplotypes of polymorphic endonuclease-restriction sites of the beta-like gene cluster (genes in the vicinity of the beta-globin gene)--one prevalent in Atlantic West Africa, another in central West Africa, and yet another in Bantu-speaking Africa (equatorial, East, and southern Africa). We have studied the differences in the hematologic characteristics of patients with sickle cell anemia from the first two geographical areas. We find that the Senegalese (Atlantic West Africa) patients have higher levels of hemoglobin F, a preponderance of G gamma chains in hemoglobin F, a lower proportion of very dense red cells, and a lower percentage of irreversibly sickled cells than those from Benin (central West Africa). We interpret these data to mean that the gamma-chain composition and the hemoglobin F level are haplotype linked and that the decrease in the percentage of dense cells and irreversibly sickled cells is secondary to the elevation in the hemoglobin F level. Patients with sickle cell anemia in the New World probably correspond to various combinations of these types, in addition to the still hematologically undefined haplotype associated with sickle cell anemia in the Bantu-speaking areas of Africa.
镰状细胞贫血患者的疾病血液学和临床特征各不相同，部分原因是修饰疾病表达的连锁和非连锁基因存在变异性。血红蛋白S基因与β样基因簇（β珠蛋白基因附近的基因）的三种不同多态性内切核酸酶限制位点单倍型紧密连锁——一种在大西洋西非地区普遍存在，另一种在中西部非洲，还有一种在讲班图语的非洲地区（赤道、东部和南部非洲）。我们研究了来自前两个地理区域的镰状细胞贫血患者血液学特征的差异。我们发现，与来自贝宁（中西部非洲）的患者相比，塞内加尔（大西洋西非）患者的血红蛋白F水平更高，血红蛋白F中Gγ链占优势，非常致密的红细胞比例更低，不可逆镰状细胞的百分比更低。我们将这些数据解释为γ链组成和血红蛋白F水平与单倍型相关，致密细胞和不可逆镰状细胞百分比的降低是血红蛋白F水平升高的继发结果。除了非洲讲班图语地区与镰状细胞贫血相关的血液学上仍未明确的单倍型外，新世界的镰状细胞贫血患者可能对应于这些类型的各种组合。
