Genotypic influence of α-deletions on the phenotype of Indian sickle cell anemia patients

Abstract

BackgroundSome reports have shown that co-inheritance of α-thalassemia and sickle cell disease improves hematological parameters and results in a relatively mild clinical picture for patients; however, the exact molecular basis and clinical significance of the interaction between α-thalassemia and sickle cell disease in India has not yet been described. There is little agreement on the clinical effects of α-thalassemia on the phenotype of sickle cell disease.MethodsComplete blood count and red cell indices were measured by an automated cell analyzer. Quantitative assessment of hemoglobin variants HbF, HbA, HbA2, and HbS was performed by high performance liquid chromatography (HPLC). DNA extraction was performed using the phenol-chloroform method, and molecular study for common α-deletions was done by gap-PCR.ResultsOut of 60 sickle cell anemia patients, the α-thalassemia genotype was found in 18 patients. Three patients had the triplicated α-genotype (Anti α-3.7 kb), and the remaining patients did not have α-deletions. This study indicates that patients with co-existing α-thalassemia and sickle cell disease had a mild phenotype, significantly improved hematological parameters, and fewer blood transfusions than the patients with sickle cell anemia without co-existing α-deletions.ConclusionCo-existence of α-thalassemia and sickle cell anemia has significant effects on the phenotype of Indian sickle cell patients.

Phenotypic Effect of α-Globin Gene Numbers on Indian Sickle β-Thalassemia Patients

“…Similar finding were reported in the patients of hemoglobin E β‐thalassemia . The finding of this study is similar to our previous report on co‐inheritance of α‐chain deletions and modulating effect on the phenotype of sickle homozygous patients . Impaired production of α‐globin chains leads to a relative excess of gamma globin chains, which is converted in β‐globin chains.…”

Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India

“…Together, the SC (1,108 castes, 16.6% of the population), ST (744 tribes, 8.6% of the population), and OBC (5,013 castes, 41% of the population) are a diverse group of endogamous communities that constitute a substantial proportion of India's population . Extensive studies of the population distribution of the β s gene in India indicate that it is most prevalent in the ST population, but is also prevalent in many SC and to a lesser extent, OBC populations . Community screening studies for SCD have previously described the distribution of β s in the SC, ST, and OBC populations in Nagpur …”

“…5,[7][8][9][10] High prevalence of the Arab-Indian globin haplotype, high hemoglobin F levels, high frequency of Xmn1 polymor-phic site, and the coinheritance of -thalassemia are putative potential genetic modifiers contributing to the milder phenotype of SCD in India. 5,8,[11][12][13][14][15][16][17][18][19][20][21] The clinical phenotype in individuals belonging to STs is reported to be milder than that observed in nontribal patients in India. 5,8,[11][12][13][14][15][16][17][18][19][20][21] The aboriginal ST populations have the highest frequencies of the s gene and often, the greatest degree of social isolation and economic disadvantage.…”

Frequencies and phenotypic consequences of association of α‐ and β‐thalassemia alleles with sickle‐cell disease in Bahrain

“…Association with α‐thalassemia leads to reduced transfusion requirement in SCD . Female patients generally required more transfusion support because of significantly lower Hb levels as well as demands imposed by pregnancy—as most patients were of child‐bearing age.…”