Molecular analysis of β-thalassemia in maldives and Japan

Abstract

Thalassemia is a group of disorders characterized by impaired expression of the -globin gene. It has a worldwide distribution with particularly high frequencies in the Mediterranean, Indian and Southeast Asian. In malaria endemic regions, the malaria hypothesis is a plausible explanation for the high prevalence of this disorder. To compare the molecular basis of the -thalassemia in between malaria endemic and non-endemic regions and to trace the origin and spread of mutations in Asian populations, we analyzed -thalassemia mutations and determined the haplotypes and frameworks in 45 Japanese -thalassemia patients and 50 Maldivian patients using PCR-related techniques. The following results were obtained. 1) In the Maldivian population, five different mutations were detected. These are IVS1#5(G-C), Codon30(G-C), IVS1#1(G-A), E and Codon41/42(-4bp). In the Japanese population, 13 different mutations were detected. These are IVS2#654(C-T), Codon90(G-T), IVS2#1(G-A), -31ATA(A-G), Codon41 /42(-4bp), Codon15(-T), Codon54(+G), Codon110(T-C), Codon123(-A), Codon127/128(-AGG), Codon121(G-T), IVS2#848(C-G) and Initiation codon(A-G). 2) Analysis of -globin gene haplotypes and frameworks suggested that most common mutation, IVS1#5(G-C) in Maldivian -thalassemia genes was derived from the Indian population, and Codon41/42(-4bp) mutation shown by both populations has different origin. 3) In the Japanese population, four dominant mutations were detected. The presence of such mutations in the Japanese population may be explained by a fact that Japan is not malaria endemic and there is a loss of heterozygous advantages against malaria infection in such mutations.