Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation

Analysis of the molecular basis of hemoglobinopathies provides an opportunity to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases referred to the counseling unit and 889 individuals from random screening of the population of Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by the PCR-ARMS method using genomic DNA. The haplotype of 56 beta(E) mutation-bearing chromosomes were identified by the RFLP-PCR method. Genotypes were constructed and correlated with hematological and clinical phenotypes. IVS-1nt 5 (G-->C) mutation was observed as the most frequent mutation, followed by codon 30 (G-->C). Production of HbE was significantly (P < 0.001) higher in nontransfusion-dependent Ebeta-thalassemia patients. beta(E) mutation was observed only on four haplotypes linked to framework 2. Type 2 haplotype was observed mainly from chromosomes of Tripura origin, but none from South Bengal. Homozygous E individuals with 1//1 genotype were significantly (P < 0.01) more anemic compared to individuals with 2//2 genotype. This work creates a database of hemoglobinopathy mutations for the population of Eastern India which will facilitate prenatal diagnosis and counseling. Am. J. Hum. Biol. 12:454-459, 2000. Copyright 2000 Wiley-Liss, Inc.