Association between sickle cell anemia and alpha thalassemia reveals a high prevalence of the α^3.7 triplication in congolese patients than in worldwide series

Abstract

Background Information about the association with alpha thalassemia in sickle cell patients is unknown in the Democratic Republic of Congo. There is very little data on the alpha thalassemia in patients suffering from sickle cell anemia in Central Africa, and their consequences on the clinical expression of the disease. Methods A cross‐sectional study was conducted in 106 sickle cell patients living in the country's capital Kinshasa. The diagnosis of sickle cell anemia was confirmed with a molecular test using PCR‐RFLP (restriction fragment length polymorphism) technique. The diagnosis of thalassemia was performed by the technique of multiplex ligation dependent probe amplification. Results The mean age of our patients was 22.4±13.6 years. The α3.7 heterozygous deletion, the α3.7 homozygous deletion and the α3.7 triplication were respectively encountered in 23.6%, 25.5% , and 11.3% of patients. Patients with normal αα/αα genotype represented 39.6% of the study population. The average of severe vaso‐occlusive crises, the rates of blood transfusions per year, the rate of osteonecrosis, cholelithiasis and leg ulcers were significantly lower in the group of patients with α3.7 homozygous deletion and α3.7 triplication. Conclusion The prevalence of α3.7 triplication was higher in sickle cell patients in the Democratic Republic of Congo than in worldwide series. The α3.7 triplication and α3.7 homozygous deletion were associated with less severe forms of the Sickle cell anemia in Congolese patients. These results showed the need to investigate systematically the alpha‐globin gene mutations in sickle cell population in Central Africa.

Influence of alpha thalassemia on clinical and laboratory parameters among nigerian children with sickle cell anemia

“…The two α‐globin genes on chromosome 16 are located within a 4‐kb duplicated region leading to the possibility of rearrangements including deletions and triplications with many attendant downstream consequences . The present study confirmed earlier reports that the 3.7 κb α‐globin gene deletion is the common α‐thal allele among Africans as none of the participants had the 4.2Kb α‐globin gene deletion.…”

“…Furthermore, as found in this study, authors from different parts of the world have reported that α‐thal protects against leg ulcer in SCA patients . However, some have reported that no such association exists .…”

“…Although several studies have described the possible effects of α‐thal among patients with SCA in the developed world, there is paucity of information about the influence of this genetic factor in African patients with SCA. Although the few available studies from Africa have established that the 3.7 κb α‐globin gene deletion is the common α‐thal allele among the African population, nonetheless, there is lack of consensus on its impacts on the laboratory and clinical manifestations of patients with SCA …”

Homozygous Deletion Alfa-Thalassemia and Hereditary Persistence of Fetal Hemoglobin, Two Genetic Factors Predictive the Reduction of Morbidity and Mortality During Pregnancy in Sickle Cell Patients . A Report From Democratic Republic of Congo

“…The protective effect of alpha-thalassemia is related to the reduction of Hb concentration in the erythrocytes, which results in the microcytic anemia 14. Indeed, Mikobi et al showed that homozygous alpha-thalassemia and an FHb level > 15% had a protective effect on SCD in Congolese patients 15. The objective of the present study was to determine the beneficial role of genetic modulating factors of sickle cell disease in fetal and maternal morbidity and mortality during pregnancy in sickle cell patients.…”

“…The diagnosis of alpha-thalassemia has been made by the Multiplex Ligation-dependent Probe Amplification (MLPA) technique. The procedures, as well as the reagents used for both techniques (RFLP and MLPA), have been carefully described by Mikobi et al 15,16…”